Assignment

Assignment 8 Olfactory receptors

Assignment 9 Photoreceptors

Assignment 10 Taste receptors

Submitted By: Muhammad Hashim

ROLL NO.58823
MSc 1st

Submitted To: Ms. Samina Yasmin

Department of Zoology
Hazara University Mansehra

DEPARTMENT OF ZOOLOGY
HAZARA UNIVERSITY MANSEHRA
2020
 Assignment 8

OLFACTORY RECEPTOR

Introduction

Olfactory receptors (ORs), also known as odorant receptors, are expressed in the cell
membranes of olfactory receptor neurons and are responsible for the detection of
odorants (i.e., compounds that have an odor) which give rise to the sense of smell.
Activated olfactory receptors trigger nerve impulses which transmit information about
odor to the brain. These receptors are members of the class A rhodopsin-like family of
G protein-coupled receptors (GPCRs). The olfactory receptors form a multigene
family consisting of around 800 genes in humans and 1400 genes in mice.

Expression

In vertebrates, the olfactory receptors are located in both the cilia and synapses of the
olfactory sensory neurons and in the epithelium of the human airway. In insects,
olfactory receptors are located on the antennae and other chemosensory organs.
Sperm cells also express odor receptors, which are thought to be involved in
chemotaxis to find the egg cell.

Mechanism

Rather than binding specific ligands, olfactory receptors display affinity for a range of
odor molecules, and conversely a single odorant molecule may bind to a number of
olfactory receptors with varying affinities, which depend on physio-chemical
properties of molecules like their molecular volumes. Once the odorant has bound to
the odor receptor, the receptor undergoes structural changes and it binds and activates
the olfactory-type G protein on the inside of the olfactory receptor neuron. The G
protein (Golf and/or Gs) in turn activates the lyase - adenylate cyclase - which
converts ATP into cyclic AMP (cAMP). The cAMP opens cyclic nucleotide-gated ion
channels which allow calcium and sodium ions to enter into the cell, depolarizing the
olfactory receptor neuron and beginning an action potential which carries the
information to the brain.
In a recent but highly controversial interpretation, it has also been speculated that
olfactory receptors might really sense various vibrational energy-levels of a molecule
rather than structural motifs via quantum coherence mechanisms. As evidence it has
been shown that flies can differentiate between two odor molecules which only differ
in hydrogen isotope (which will drastically change vibrational energy levels of the
molecule). Not only could the flies distinguish between the deuterated and non-
deuterated forms of an odorant, they could generalise the property of "deuteratedness"
to other novel molecules. In addition, they generalised the learned avoidance
behaviour to molecules which were not deuterated but did share a significant vibration
stretch with the deuterated molecules, a fact which the differential physics of
deuteration (below) has difficulty in accounting for.

It has been claimed that human olfactory receptors are capable of distinguishing
between deuterated and undeuterated isotopomers of cyclopentadecanone by
vibrational energy level sensing. However this claim has been challenged by another
report that the human musk-recognizing receptor, OR5AN1 that robustly responds to
cyclopentadecanone and muscone, fails to distinguish isotopomers of these
compounds in vitro. Furthermore, the mouse (methylthio)methanethiol-recognizing
receptor, MOR244-3, as well as other selected human and mouse olfactory receptors,
responded similarly to normal, deuterated, and carbon-13 isotopomers of their
respective ligands, paralleling results found with the musk receptor OR5AN1. Hence
it was concluded that the proposed vibration theory does not apply to the human musk
receptor OR5AN1, mouse thiol receptor MOR244-3, or other olfactory receptors
examined. In addition, the proposed electron transfer mechanism of the vibrational
frequencies of odorants could be easily suppressed by quantum effects of nonodorant
molecular vibrational modes. Hence multiple lines of evidence argue against the
vibration theory of smell. This later study was criticized since it used "cells in a dish
rather than within whole organisms" and that "expressing an olfactory receptor in
human embryonic kidney cells doesn't adequately reconstitute the complex nature of
olfaction...". In response, the authors of the second study state "Embryonic kidney
cells are not identical to the cells in the nose .. but if you are looking at receptors, it's
the best system in the world."
Malfunction of the metalloproteins in the olfactory system is hypothesized to have a
connection with amyloidal based neurodegenerative diseases.

Diversity

There are a large number of different odor receptors, with as many as 1,000 in the
mammalian genome which represents approximately 3% of the genes in the genome.
However, not all of these potential odor receptor genes are expressed and functional.
According to an analysis of data derived from the Human Genome Project, humans
have approximately 400 functional genes coding for olfactory receptors, and the
remaining 600 candidates are pseudogenes.

Deorphanization of odor receptors can be completed using electrophysiological and

imaging techniques to analyze the response profiles of single sensory neurons to odor
repertoires. Such data open the way to the deciphering of the combinatorial code of
the perception of smells.

Families

A nomenclature system has been devised for the olfactory receptor family[32] and is
the basis for the official Human Genome Project (HUGO) symbols for the genes that
encode these receptors. The names of individual olfactory receptor family members
are in the format "ORnXm" where:

1. OR is the root name (Olfactory Receptor superfamily)

2. n = an integer representing a family (e.g., 1-56) whose members have greater
than 40% sequence identity,
3. X = a single letter (A, B, C, ...) denoting a subfamily (>60% sequence
identity), and
4. m = an integer representing an individual family member (isoform).
5. For example, OR1A1 is the first isoform of subfamily A of olfactory receptor
family 1.

Members belonging to the same subfamily of olfactory receptors (>60% sequence

identity) are likely to recognize structurally similar odorant molecules.[33]
Two major classes of olfactory receptors have been identified in humans:

Evolution

The olfactory receptor gene family in vertebrates has been shown to evolve through
genomic events such as gene duplication and gene conversion. Evidence of a role for
tandem duplication is provided by the fact that many olfactory receptor genes
belonging to the same phylogenetic clade are located in the same gene cluster. To this
point, the organization of OR genomic clusters is well conserved between humans and
mice, even though the functional OR count is vastly different between these two
species. Such birth-and-death evolution has brought together segments from several
OR genes to generate and degenerate odorant binding site configurations, creating
new functional OR genes as well as pseudogenes.

Compared to many other mammals, primates have a relatively small number of

functional OR genes. For instance, since divergence from their most recent common
ancestor (MRCA), mice have gained a total of 623 new OR genes, and lost 285 genes,
whereas humans have gained only 83 genes, but lost 428 genes. Mice have a total of
1035 protein-coding OR genes, humans have 387 protein-coding OR genes. The
vision priority hypothesis states that the evolution of color vision in primates may
have decreased primate reliance on olfaction, which explains the relaxation of
selective pressure that accounts for the accumulation of olfactory receptor
pseudogenes in primates. However, recent evidence has rendered the vision priority
hypothesis obsolete, because it was based on misleading data and assumptions. The
hypothesis assumed that functional OR genes can be correlated to the olfactory
capability of a given animal.In this view, a decrease in the fraction of functional OR
genes would cause a reduction in the sense of smell; species with higher pseudogene
count would also have a decreased olfactory ability. This assumption is flawed. Dogs,
which are reputed to have good sense of smell, do not have the largest number of
functional OR genes. Additionally, pseudogenes may be functional; 67% of human
OR pseudogenes are expressed in the main olfactory epithelium, where they possibly
have regulatory roles in gene expression. More importantly, the vision priority
hypothesis assumed a drastic loss of functional OR genes at the branch of the OWMs,
but this conclusion was biased by low-resolution data from only 100 OR genes. High-
resolution studies instead agree that primates have lost OR genes in every branch
from the MRCA to humans, indicating that the degeneration of OR gene repertories in
primates cannot simply be explained by the changing capabilities in vision.

It has been shown that negative selection is still relaxed in modern human olfactory
receptors, suggesting that no plateau of minimal function has yet been reached in
modern humans and therefore that olfactory capability might still be decreasing. This
is considered to provide a first clue to the future human genetic evolution.

Discovery

In 2004 Linda B. Buck and Richard Axel won the Nobel Prize in Physiology or
Medicine for their work on olfactory receptors. In 2006, it was shown that another
class of odorant receptors – known as trace amine-associated receptors (TAARs) –
exist for detecting volatile amines. Except for TAAR1, all functional TAARs in
humans are expressed in the olfactory epithelium. A third class of olfactory receptors
known as vomeronasal receptors has also been identified; vomeronasal receptors
putatively function as pheromone receptors.

As with many other GPCRs, there is still a lack of experimental structures at atomic
level for olfactory receptors and structural information is based on homology
modeling methods.

The limited functional expression of olfactory receptors in heterologous systems,

however, has greatly hampered attempts to deorphanize them (analyze the response
profiles of single olfactory receptors). This was first completed by genetically
engineered receptor, OR-I7 to characterize the ―odor space‖ of a population of native
aldehyde receptors.
References

Gaillard I, Rouquier S, Giorgi D (February 2004). "Olfactory receptors". Cellular and

Molecular Life Sciences. 61 (4): 456–69. doi:10.1007/s00018-003-3273-7.
PMID 14999405.

Hussain A, Saraiva LR, Korsching SI (March 2009). "Positive Darwinian selection

and the birth of an olfactory receptor clade in teleosts". Proceedings of the
National Academy of Sciences of the United States of America. 106 (11):
4313–8. Bibcode:2009PNAS..106.4313H. doi:10.1073/pnas.0803229106.
PMC 2657432. PMID 19237578.

Niimura Y (December 2009). "Evolutionary dynamics of olfactory receptor genes in

chordates: interaction between environments and genomic contents". Human
Genomics. 4 (2): 107–18. doi:10.1186/1479-7364-4-2-107. PMC 3525206.
PMID 20038498.

Rinaldi A (July 2007). "The scent of life. The exquisite complexity of the sense of
smell in animals and humans". EMBO Reports. 8 (7): 629–33.
doi:10.1038/sj.embor.7401029. PMC 1905909. PMID 17603536.

Gu X, Karp PH, Brody SL, Pierce RA, Welsh MJ, Holtzman MJ, Ben-Shahar Y
(March 2014). "Chemosensory functions for pulmonary neuroendocrine cells".
American Journal of Respiratory Cell and Molecular Biology. 50 (3): 637–46.
doi:10.1165/rcmb.2013-0199OC. PMC 4068934. PMID 24134460.

Hallem EA, Dahanukar A, Carlson JR (2006). "Insect odor and taste receptors".
Annual Review of Entomology. 51: 113–35.
 Assignment 9

Photoreceptors

Introduction

Photoreceptors are the cells in the retina that respond to light. Their distinguishing
feature is the presence of large amounts of tightly packed membrane that contains the
photopigment rhodopsin or a related molecule. The tight packing is needed to achieve
a high photopigment density, which allows a large proportion of the light photons that
reach the photoreceptor to be absorbed. Photon absorption contributes to the
photoreceptor’s output signal.

In the retina of vertebrates the rods and cones have photopigment-bearing regions
(outer segments) composed of a large number of pancakelike disks. In rods the disks
are closed, but in cones the disks are partially open to the surrounding fluid. In a
typical rod there are about a thousand disks, and each disk holds about 150,000
rhodopsin molecules, giving a total of 150 million molecules per rod. In most
invertebrate photoreceptors the structure is different, with the photopigment borne on
regularly arranged microvilli, fingerlike projections with a diameter of about 0.1 μm.
This photoreceptor structure is known as a rhabdom. The photopigment packing is
less dense in rhabdoms than in vertebrate disks. In both vertebrate photoreceptors and
rhabdoms, each photoreceptor cell contains a nucleus, an energy-producing region
with mitochondria (in the inner segment in rods and cones), and an axon that conveys
electrical signals to the next neurons in the processing chain. In reptiles and birds the
receptors may also contain coloured oil droplets that modify the spectrum of the light
absorbed by the photopigment, thereby enhancing colour vision. In insects and other
invertebrates the receptors may also contain granules of dark pigment that move
toward the rhabdom in response to light. They act as a type of pupil, protecting the
rhabdom in bright conditions by absorbing light.

Photo pigments

The photopigments that absorb light all have a similar structure, which consists of a
protein called an opsin and a small attached molecule known as the chromophore. The
chromophore absorbs photons of light, using a mechanism that involves a change in
its configuration. In vertebrate rods the chromophore is retinal, the aldehyde of
vitamin A1. When retinal absorbs a photon, the double bond between the 11th and
12th carbon atoms flips, thus reconfiguring the molecule from the 11-cis to the all-
trans form. This in turn triggers a molecular transduction cascade, resulting in the
closure of sodium channels in the membrane and hyperpolarization (increase in
negativity) of the cell. Retinal then detaches from opsin, is regenerated to the 11-cis
state in the cells of the pigment epithelium that surround the rods, and is reattached to
an opsin molecule. In most invertebrate photoreceptors the chromophore does not
detach from opsin but is regenerated in situ, usually by the absorption of a photon
with a wavelength different from the stimulating wavelength.

Most perceived colours are interpreted by the brain from a ratio of excitation in
different cone types. The fact that the spectral sensitivity maxima of the M and L
cones are very close together reveals an interesting evolutionary history. Most fish
and birds have four or even five cone types with different spectral sensitivities,
including sensitivity in the ultraviolet. In contrast, most mammals have only two—an
S cone for blue wavelengths and an L cone for red wavelengths. Thus, these mammals
have dichromatic vision, and they are red-green colour-blind. The relative poverty of
the mammalian colour system is probably due to the way that the early mammals
survived the age of reptiles by adopting a nocturnal and even subterranean way of life
in which colour vision was impossible. However, about 63 million years ago a
mutation in the genotype of the Old World primates resulted in the duplication of the
gene for the long-wavelength opsin, which provided another channel for a
trichromatic colour vision system. The red-green system of M and L cones enabled
primates to distinguish particular elements in their environment—for example, the
ripeness of fruit in the tropical woodlands that the early primates inhabited.

Neural transmission

All vertebrates have complex retinas with five layers, first described in detail by
Spanish histologist Santiago Ramón y Cajal in the 1890s. There are three layers of
cells on the pathway from the photoreceptors to the optic nerve. These are the
photoreceptors themselves at the rear of the retina, the bipolar cells, and finally the
ganglion cells, whose axons make up the optic nerve. Forming a network between
the photoreceptors and the bipolar cells are the horizontal cells (the outer plexiform
layer), and between the bipolar cells and the ganglion cells, there exists a similar
layer (the inner plexiform layer) containing amacrine cells of many different kinds. A
great deal of complex processing occurs within the two plexiform layers. The main
function of the horizontal cells is to vary the extent of coupling between
photoreceptors and between photoreceptors and bipolar cells. This provides a control
system that keeps the activity of the bipolar cells within limits, regardless of
fluctuations in the intensity of light reaching the receptors. This control process also
enhances contrast, thus emphasizing the differences between photoreceptor outputs.

In dark conditions, cGMP binds to sodium channels in the cell membrane, keeping the
channels open and allowing sodium ions to enter the cell continuously. The constant
influx of positive sodium ions maintains the cell in a somewhat depolarized (weakly
negative) state. In light conditions, cGMP does not bind to the channels, which allows
some sodium channels to close and cuts off the inward flow of sodium ions. The
reduction in influx of sodium ions causes the cell to become hyperpolarized (strongly
negative). Thus, the electrical effect of a photon of light is to cause a short-lived
negative potential in the photoreceptor. Bright light produces more rhodopsin
isomerizations, further decreasing cGMP levels and enabling hyperpolarization to be
graded with light intensity. The electrical signal produced by light reaches the base of
the inner segment of the receptor, where a neuronal synapse releases vesicles of
neurotransmitter (in this case glutamate) in proportion to voltage in the receptor. In
humans and other vertebrates, neurotransmitter release occurs in the dark (when the
photoreceptor plasma membrane is depolarized). In the presence of light, however,
the cell becomes hyperpolarized, and neurotransmitter release is inhibited.

In invertebrate eyes the electrical response to light is different. The majority of

invertebrate eyes have microvillus receptors that depolarize (become less negative)
when illuminated—the opposite of the response in vertebrate receptors. The
depolarization is brought about by the entry of sodium and calcium ions that results
from the opening of membrane channels. The biochemistry of the transducer pathway
is not entirely clear; some proposed models envision a somewhat different pathway
from that in vertebrates. Rhodopsin isomerization activates a G-protein, which in turn
activates an enzyme called phospholipase C (PLC). PLC catalyzes the production of
an intracellular second messenger known as IP3 (inositol 1,4,5-trisphosphate), which
stimulates the release of calcium from intracellular stores in certain organelles. It is
not entirely clear what causes the membrane channels to open; however, there is
evidence that calcium plays a major role in this process. In contrast to other
invertebrates, the ―off‖-responding distal receptors of the scallop retina work by a
different mechanism. They hyperpolarize to light (similar to vertebrate receptors) by
closing sodium channels, which also results in the simultaneous release of potassium
ions from cells.

Adaptive Mechanisms Of Vision

The human visual system manages to provide a usable signal over a broad range of
light intensities. However, some eyes are better adapted optically to dealing with light
or dark conditions. For example, the superposition eyes of nocturnal moths may be as
much as a thousand times more sensitive than the apposition eyes of diurnal
butterflies. Within vertebrate eyes, there are four kinds of mechanisms that operate to
allow vision across a wide range of light intensities. These include mechanisms
specific to the iris, the splitting of the intensity range between rods and cones,
adjustments to the signal transduction process in the photoreceptors, and variations in
the availability of active photopigment molecules.

Vision and light intensity

The most obvious mechanism involved in light regulation is the iris. In humans the
iris opens in the dark to a maximum diameter of 8 mm (0.31 inch) and closes to a
minimum of 2 mm (0.08 inch). The image brightness in the retina changes by a factor
of 16. In other animals the effect of the pupil may be much greater; for example, in
certain geckos the slit pupil can close from a circle of several millimetres in diameter
down to four pinholes each, with a diameter of 0.1 mm (0.004 inch) or less. The
retinal brightness ratio is at least a thousandfold. The reason for this great range is
probably that the gecko’s nocturnal eye needs strong protection from bright daylight.

In humans the rods are concerned with the dimmest part of the eye’s working range
and have no colour vision. The cones begin to take over at about the level of bright
moonlight, and at all daylight intensities the cones alone provide the visual signal.
Rods respond to single photons of light with large electrical signals, which means that
the electrical responses saturate at low rates of photon capture by the rhodopsin
molecules. Rods operate over the range from the threshold of vision, when they are
receiving about one photon every 85 minutes, to dawn and dusk conditions, when
they receive about 100 photons per second. For most of their range the rods are
signaling single photon captures. The cones are much less sensitive than the rods; they
still respond to single photons, but the sizes of the resulting electrical signals are
much smaller. This gives the cones a much larger working range, from a minimum of
about three photons per second to more than a million per second, which is enough to
deal with the brightest conditions that humans encounter.

If cones are presented with brief flashes, rather than steady illumination changes, their
working range from threshold to saturation is small—reduced to a factor of about 100.
However, longer illumination induces two kinds of change that extend this range. The
biochemical transducer cascade that leads to the electrical signal has an ability to
regulate its own gain, thereby reducing the size of the electrical signal at high photon
capture rates. The main mechanism depends on the fact that calcium ions, which enter
the photoreceptor along with sodium ions, have an inhibitory effect on the synthesis
of cGMP, the molecule that keeps the sodium channels open (see above Structure and
function of photoreceptors: Neural transmission). The effect of light is to reduce
cGMP levels and thus close the membrane channels to sodium and calcium. If the
light is persistent, calcium levels in the photoreceptor fall, the calcium ―brake‖ on
cGMP production weakens, and cGMP levels increase somewhat. Increased cGMP
production opens the membrane channels again. Thus, there is a feedback loop that
tends to oppose the direct effect of light, ensuring that saturation (complete closure of
all the membrane channels) does not occur. This in turn extends the top end of the
photoreceptor’s working range.

The slow speed of turnover of functional visual pigment molecules also helps to
extend the eye’s ability to respond to high light levels. In vertebrates the all-trans
retinal, produced when a photon isomerizes the 11-cis retinal of a rhodopsin molecule,
is removed from the rod or cone. It passes to the adjacent pigment epithelium, where
it is regenerated back to the active 11-cis form and passed back to the photoreceptor.
On average, this process takes two minutes. The higher the light level, the greater the
number of molecules of retinal in the inactive all-trans state. Therefore, there are
fewer rhodopsin molecules available to respond to light. At the top end of the
intensity distribution, photoreception becomes self-limiting, with the cones never
catching more than about one million photons per second.
Eye movements and active vision

There are four main types of eye movement: saccades, reflex stabilizing movements,
pursuit movements, and vergence movements. Saccades are fast movements that
redirect gaze. They may involve the eyes alone or, more commonly, the eyes and the
head. Their function is to place the fovea (the central region of the retina where vision
is most acute) onto the images of parts of the visual scene of interest. The duration
and peak velocity of saccades vary systematically with their size. The smallest
movements, microsaccades, move the eye through only a few minutes of arc. They
last about 20 milliseconds and have maximum velocities of about 10 degrees per
second. The largest saccades (excluding the contributions of head movements) can be
up to 100 degrees, with a duration of up to 300 milliseconds and a maximum velocity
of about 500–700 degrees per second. During saccades, vision is seriously impaired
for two reasons. First, during large saccades, the image is moving so fast that it is
blurred and unusable. Second, an active blanking-off process, known as saccadic
suppression, occurs, and this blocks vision for the first part of each saccade. Between
saccades, the eyes are held stationary in fixations. It is during these periods, which
last on average about 190 milliseconds, that the eye takes in visual information.
Saccades can be reflexive in nature—for example, when an object appears in one’s
peripheral field of view. However, as Russian psychologist Alfred L. Yarbus showed,
saccades are often information-seeking in nature, directed to particular objects or
regions by the requirements of ongoing behaviour.

During fixations the eyes are stabilized against movements of the head and body by
two reflexes, the vestibulo-ocular reflex (VOR) and the optokinetic reflex (OKR). In
VOR the semicircular canals of the inner ear measure rotation of the head and provide
a signal for the oculomotor nuclei of the brainstem, which innervate the eye muscles.
The muscles counterrotate the eyes in such a way that a rightward head rotation
causes an equal leftward rotation of both eyes, with the result that gaze direction stays
stationary. OKR is a feedback loop in which velocity-sensitive ganglion cells in the
retina feed a signal, via the oculomotor nuclei, to the eye muscles. The effect of the
feedback loop is to move the eye in the same direction as the image motion. With a
moving background (e.g., when looking out of a train window), OKR ensures that the
eye moves at almost the same speed as the image, and the result is optokinetic
nystagmus, a sawtooth motion in which OKR alternates with saccadelike movements
that reset the eyes to a central position. However, the principal function of OKR is to
keep gaze stationary by nulling out any involuntary motion that results from visual
drift or slow head movement. In general OKR and VOR work together to keep the
image stationary on the retina, with VOR compensating for fast movements and OKR
for slower movements. Humans and other primates have the ability to track moving
objects with their eyes; this capacity is not widespread in mammals or other
vertebrates. These tracking movements employ a velocity feedback loop (similar to
OKR) that functions only for small centrally placed targets (unlike OKR, which
works over a much wider field). Smooth tracking, in which the eye moves
continuously with the target, is typically confined to slow speeds (less than 20 degrees
per second), although it sometimes can match targets moving up to 90 degrees per
second. For faster objects the eye lags behind the target and catches up to it by using
saccades. Thus, when watching a tennis match, the eyes track the ball with a mixed
strategy of smooth movements and saccades.

Vergence movements occur as an object approaches or recedes from the observer.

They differ from other eye movements in that the two eyes move in opposite
directions. Vergence movements are confined to humans and other animals with
frontal eyes that employ binocular mechanisms to determine distance.

The saccade-and-fixate strategy is the way humans take in information from the world
most of the time. However, there is a mismatch between the extremely jerky
movements of the image on the retina and the apparently smooth and coherent view of
the world that is perceived consciously. While there is no scientific explanation for
this discrepancy, it is clear that humans retain little information from one fixation to
the next. If observers are presented with alternating views of the same scene, but with
one substantial change between views, it takes many presentations before the change
is detected if a blank period equivalent to a saccade is introduced between each view.
However, if there is no blank period, the change is readily detected because it
produces a visible local change in the image, which attracts attention. This
phenomenon, known as change blindness, seems to imply that one reason humans do
not ―see‖ saccades is that the preceding image is not retained. Thus, humans have no
basis for detecting the change that each saccade causes.
References

"eye, human." Encyclopædia Britannica. Encyclopædia Britannica Ultimate

Reference Suite. Chicago: Encyclopædia Britannica, 2010.

Foster, R.G.; Provencio, I.; Hudson, D.; Fiske, S.; Grip, W.; Menaker, M. (1991).
"Circadian photoreception in the retinally degenerate mouse (rd/rd)". Journal
of Comparative Physiology A. 169 (1): 39–50. doi:10.1007/BF00198171.
PMID 1941717.

Hecht, S.; Shlar, S.; Pirenne, M.H. (1942). "Energy, Quanta, and Vision". Journal of
General Physiology. 25 (6): 819–840. doi:10.1085/jgp.25.6.819. PMC
2142545. PMID 19873316.

Baylor, D.A.; Lamb, T.D.; Yau, K.W. (1979). "Responses of retinal rods to single
photons". The Journal of Physiology. 288: 613–634.
doi:10.1113/jphysiol.1979.sp012716 (inactive 2020-01-22). PMC 1281447.
PMID 112243.

Hurvich, Leo (1981). Color Vision. Sinauer.

"Owl Eye Information". owls.org. World Owl Trust. Retrieved 1 May 2017.

"Scientists document light-sensitive birds eye within bird brain". birdsnews.com.

Birds News. Archived from the original on 2 July 2017. Retrieved 20 July
2017.

Human Physiology and Mechanisms of Disease by Arthur C. Guyton (1992) ISBN 0-

7216-3299-8 p. 373
 Assignment 10

Taste receptor

A taste receptor is a type of receptor which facilitates the sensation of taste. When food or
other substances enter the mouth, molecules interact with saliva and are bound to taste
receptors in the oral cavity and other locations. Molecules which give a sensation of taste are
considered "sapid".

Visual, olfactive, "sapictive" (the perception of tastes), trigeminal (hot, cool), mechanical, all
contribute to the perception of taste. Of these, transient receptor potential cation channel
subfamily V member 1 (TRPV1) vanilloid receptors are responsible for the perception of
heat from some molecules such as capsaicin, and a CMR1 receptor is responsible for the
perception of cold from molecules such as menthol, eucalyptol, and icilin.

Tissue distribution

The gustatory system consists of taste receptor cells in taste buds. Taste buds, in turn, are
contained in structures called papillae. There are three types of papillae involved in taste:
fungiform papillae, foliate papillae, and circumvallate papillae. (The fourth type - filiform
papillae do not contain taste buds). Beyond the papillae, taste receptors are also in the palate
and early parts of the digestive system like the larynx and upper esophagus. There are three
cranial nerves that innervate the tongue; the vagus nerve, glossopharyngeal nerve, and the
facial nerve. The glossopharyngeal nerve and the chorda tympani branch of the facial nerve
innervate the TAS1R and TAS2R taste receptors. Next to the taste receptors in on the
tongue, the gut epithelium is also equipped with a subtle chemosensory system that
communicates the sensory information to several effector systems involved in the regulation
of appetite, immune responses, and gastrointestinal motility

In 2010, researchers found bitter receptors in lung tissue, which cause airways to relax when
a bitter substance is encountered. They believe this mechanism is evolutionarily adaptive
because it helps clear lung infections, but could also be exploited to treat asthma and chronic
obstructive pulmonary disease.

Function

Taste helps to identify toxins, maintain nutrition, and regulate appetite, immune responses,
and gastrointestinal motility. Five basic tastes are recognized today: salty, sweet, bitter, sour,
and umami. Salty and sour taste sensations are both detected through ion channels. Sweet,
bitter, and umami tastes, however, are detected by way of G protein-coupled taste receptors.
Mechanism of action

The standard bitter, sweet, or umami taste receptor is a G protein-coupled receptor with
seven transmembrane domains. Ligand binding at the taste receptors activate second
messenger cascades to depolarize the taste cell. Gustducin is the most common taste Gα
subunit, having a major role in TAS2R bitter taste reception. Gustducin is a homologue for
transducin, a G-protein involved in vision transduction. Additionally, taste receptors share
the use of the TRPM5 ion channel, as well as a phospholipase PLCβ2.

Savory or glutamates (Umami)

The TAS1R1+TAS1R3 heterodimer receptor functions as an umami receptor, responding to

L-amino acid binding, especially L-glutamate. The umami taste is most frequently
associated with the food additive monosodium glutamate (MSG) and can be enhanced
through the binding of inosine monophosphate (IMP) and guanosine monophosphate (GMP)
molecules.[10][11] TAS1R1+3 expressing cells are found mostly in the fungiform papillae
at the tip and edges of the tongue and palate taste receptor cells in the roof of the mouth.
These cells are shown to synapse upon the chorda tympani nerves to send their signals to the
brain, although some activation of the glossopharyngeal nerve has been found.

Sweet

The diagram above depicts the signal transduction pathway of the sweet taste. Object A is a
taste bud, object B is one taste cell of the taste bud, and object C is the neuron attached to
the taste cell. I. Part I shows the reception of a molecule. 1. Sugar, the first messenger, binds
to a protein receptor on the cell membrane. II. Part II shows the transduction of the relay
molecules. 2. G Protein-coupled receptors, second messengers, are activated. 3. G Proteins
activate adenylate cyclase, an enzyme, which increases the cAMP concentration.
Depolarization occurs. 4. The energy, from step 3, is given to activate the K+, potassium,
protein channels.III. Part III shows the response of the taste cell. 5. Ca+, calcium, protein
channels is activated.6. The increased Ca+ concentration activates neurotransmitter vesicles.
7. The neuron connected to the taste bud is stimulated by the neurotransmitters.

The TAS1R2+TAS1R3 heterodimer receptor functions as the sweet receptor by binding to a

wide variety of sugars and sugar substitutes. TAS1R2+3 expressing cells are found in
circumvallate papillae and foliate papillae near the back of the tongue and palate taste
receptor cells in the roof of the mouth. These cells are shown to synapse upon the chorda
tympani and glossopharyngeal nerves to send their signals to the brain. The TAS1R3
homodimer also functions as a sweet receptor in much the same way as TAS1R2+3 but has
decreased sensitivity to sweet substances. Natural sugars are more easily detected by the
TAS1R3 receptor than sugar substitutes. This may help explain why sugar and artificial
sweeteners have different tastes. Genetic polymorphisms in TAS1R3 partly explain the
difference in sweet taste perception and sugar consumption between people of African
American ancestry and people of European and Asian ancestries.

Bitter

The TAS2R proteins (InterPro: IPR007960) function as bitter taste receptors. There are 43
human TAS2R genes, each of which (excluding the five pseudogenes) lacks introns and
codes for a GPCR protein.[7] These proteins, as opposed to TAS1R proteins, have short
extracellular domains and are located in circumvallate papillae, palate, foliate papillae, and
epiglottis taste buds, with reduced expression in fungiform papillae. Though it is certain that
multiple TAS2Rs are expressed in one taste receptor cell, it is still debated whether
mammals can distinguish between the tastes of different bitter ligands. Some overlap must
occur, however, as there are far more bitter compounds than there are TAS2R genes.
Common bitter ligands include cycloheximide, denatonium, PROP (6-n-propyl-2-thiouracil),
PTC (phenylthiocarbamide), and β-glucopyranosides.

Signal transduction of bitter stimuli is accomplished via the α-subunit of gustducin. This G
protein subunit activates a taste phosphodiesterase and decreases cyclic nucleotide levels.
Further steps in the transduction pathway are still unknown. The βγ-subunit of gustducin
also mediates taste by activating IP3 (inositol triphosphate) and DAG (diglyceride). These
second messengers may open gated ion channels or may cause release of internal calcium.
Though all TAS2Rs are located in gustducin-containing cells, knockout of gustducin does
not completely abolish sensitivity to bitter compounds, suggesting a redundant mechanism
for bitter tasting[9] (unsurprising given that a bitter taste generally signals the presence of a
toxin).[9] One proposed mechanism for gustducin-independent bitter tasting is via ion
channel interaction by specific bitter ligands, similar to the ion channel interaction which
occurs in the tasting of sour and salty stimuli.
One of the best-researched TAS2R proteins is TAS2R38, which contributes to the tasting of
both PROP and PTC. It is the first taste receptor whose polymorphisms are shown to be
responsible for differences in taste perception. Current studies are focused on determining
other such taste phenotype-determining polymorphisms. More recent studies show that
genetic polymorphisms in other bitter taste receptor genes influence bitter taste perception of
caffeine, quinine and denatonium benzoate.

Sour

Historically it was thought that the sour taste was produced solely when free hydrogen ions
(H+) directly depolarised taste receptors. However, specific receptors for sour taste with
other methods of action are now being proposed. HCN1 and HCN4 (HCN channels) were
two such proposals; both of these receptors are cyclic nucleotide-gated channels. The two
ion channels suggested to contribute to sour taste are ACCN1 and TASK-1.The diagram
depicts the signal transduction pathway of the sour or salty taste. Object A is a taste bud,
object B is a taste receptor cell within object A, and object C is the neuron attached to object
B. I. Part I is the reception of hydrogen ions or sodium ions. 1. If the taste is sour, H+ ions,
from an acidic substances, pass through their specific ion channel. Some can go through the
Na+ channels. If the taste is salty Na+, sodium, molecules pass through the Na+ channels.
Depolarization takes place II. Part II is the transduction pathway of the relay molecules.2.
Cation, such as K+, channels are opened. III. Part III is the response of the cell. 3. An influx
of Ca+ ions is activated.4. The Ca+ activates neurotransmitters. 5. A signal is sent to the
neuron attached to the taste bud.

Salt

Various receptors have also been proposed for salty tastes, along with the possible taste
detection of lipids, complex carbohydrates, and water. Evidence for these receptors is,
however, shaky at best, and is often unconvincing in mammal studies. For example, the
proposed ENaC receptor for sodium detection can only be shown to contribute to sodium
taste in Drosophilia.

Carbonation

An enzyme connected to the sour receptor transmits information about carbonated water.
 Fat

A possible taste receptor for fat, CD36, has been identified. CD36 has been localized to the
circumvallate and foliate papillae, which are present in taste buds and where lingual lipase is
produced, and research has shown that the CD36 receptor binds long chain fatty acids.
Differences in the amount of CD36 expression in human subjects were associated with their
ability to taste fats, creating a case for the receptor's relationship to fat tasting. Further
research into the CD36 receptor could be useful in determining the existence of a true fat-
tasting receptor.
References

This, Hervé (2012). "The Science of the Oven - Excerpt from Chapter 1". Retrieved 30 Apr
2014.

Nelson G, Hoon MA, Chandrashekar J, Zhang Y, Ryba NJ, Zuker CS (August 2001).
"Mammalian sweet taste receptors". Cell. 106 (3): 381–90. doi:10.1016/S0092-
8674(01)00451-2. PMID 11509186.

Adler E, Hoon MA, Mueller KL, Chandrashekar J, Ryba NJ, Zuker CS (March 2000). "A
novel family of mammalian taste receptors". Cell. 100 (6): 693–702.
doi:10.1016/S0092-8674(00)80705-9. PMID 10761934.

http://bitterdb.agri.huji.ac.il/dbbitter.php#receptorBrowse

Steensels S, Depoortere I (2018). "Chemoreceptors in the Gut". Annual Review of

Physiology. 80: 117–141. doi:10.1146/annurev-physiol-021317-121332. PMID
29029594.

Deshpande DA, Wang WC, McIlmoyle EL, Robinett KS, Schillinger RM, An SS, Sham JS,
Liggett SB (November 2010). "Bitter taste receptors on airway smooth muscle
bronchodilate by localized calcium signaling and reverse obstruction". Nature
Medicine. 16 (11): 1299–304. doi:10.1038/nm.2237. PMC 3066567. PMID
20972434.

Bachmanov AA, Beauchamp GK (2007). "Taste receptor genes". Annual Review of

Nutrition. 27: 389–414. doi:10.1146/annurev.nutr.26.061505.111329. PMC 2721271.
PMID 17444812.