A/ProfLesleyLluka

BIOL1040
MODULE1:PRINCIPLESOFCELL
FUNCTION
CellCommunication&ReceptorFamilies
AssociateProfessorLesleyJ.Lluka
SchoolofBiomedicalSciences
TheUniversityofQueensland
L.Lluka@uq.edu.au
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 Biohorizons PlenaryLecture
Aconferencefor1st yearbiologystudentsinBIOL1040
SchoolofBiomedicalSciences
Saturday19th March
9:45am12:30pm,UQCentre
Targeting cancer specific defects to selectively
destroy your tumour

Professor
Brian Gabrielli
Cancer Program Head
Diamantina Institute
The University of
Queensland
 A/ProfLesleyLluka

MODULE1:
PRINCIPLESOFCELLFUNCTION
MembraneStructure&Function
CellCommunication&ReceptorFamilies
Review&Application UQCentreWorkshops:
14th March
11th April(withModule2)

7
 A/ProfLesleyLluka

CellCommunication:
LearningObjectives
Describethetypesofcelltocellcommunication
Listanddescribeingeneraltermsthe3stagesof
cellsignalling
Brieflycompareandcontrastthe4familiesof
receptors
Explaintheconceptofsignalamplification
DescribehowGproteincoupledreceptors
producearesponseinacell
Rationalise theeffectsofinsulinatthereceptor
andcellularlevel
 A/ProfLesleyLluka
ResourcesrelevanttoCell
Communication
Campbelletal.Biology, 10th edn,2014 Chpt 11
Concept11.1:Externalsignalsareconvertedtoresponses
withinthecell
Concept11.2:Reception:Asignalling moleculebindstoa
receptorprotein,causingittochangeshape
Concept11.3:Transduction:Cascadesofmolecular
interactionsrelaysignalsfromreceptorstotargetmolecules
inthecell
Concept11.4:Response:Cellsignalling leadstoregulation
oftranscriptionorcytoplasmic activities
 Celltocellcommunication:Localvs.
longdistancesignalling
part of nerve
signalling from origin
to this point is long
distance

can be different organ

target cell: another nerve cell/muscle cell

one type not here: autocrine signalling, cell releases a substance which
works back on itself, receptors on cell that released it

Fig. 11.5 Campbell et al. 2014

 Celltocellcommunication:3stagesof
cellsignalling

a protein

receptor has
different shape for
different
signalling
molecules

regardless of distance
signalling molecule travelled

Fig. 11.6 Campbell et al. 2014

 Hormone/Ligand/Agonistactvia
receptors
carrier protein bc hard to move around
hydrophilic signalling in blood, since it is hydrophobic
molecule doesnt move across
membrane easily, interacts
Carrier protein
with receptor outside the cell
transmembrane
receptors (embedded
Small hydrophobic
in the cell membrane) applies to 3 families of receptors signalling molecule
cell-surface need signalling molecule
to get inside cell since
receptor
Y
receptor is intracellular

one family of receptors

need hydrophobic
signalling molecule

Intracellular
receptor
Response e.g. gene activation, enzyme stimulation,
rearrange cytoskeleton
 A/ProfLesleyLluka
ResourcesrelevanttoCell
Communication
Campbelletal.Biology, 10th edn,2014 Chpt 11
Concept11.1:Externalsignalsareconvertedtoresponses
withinthecell
Concept11.2:Reception:Asignalling moleculebindstoa
receptorprotein,causingittochangeshape
Concept11.3:Transduction:Cascadesofmolecular
interactionsrelaysignalsfromreceptorstotargetmolecules
inthecell
Concept11.4:Response:Cellsignalling leadstoregulation
oftranscriptionorcytoplasmic activities
top receptor here is the fastest, bottom is
slowest, so ion channel receptors fastest,
steroid receptors slowest
Receptortypes
Plasma Membrane Receptors
like ion channels before, but this is particular type of ion channel is a receptor

Ion channel receptors: needs a ligand/neurotransmitter to

open the channel up
- Na channel opened by ligand e.g. nictoninc
+

receptors fast neurotransmission milliseconds, suitable for nerves

consist of long chain of amino acids that bends itself in
huge family, 1500, very important receptor and out of the cell membrane exactly 7 times
G protein-coupled receptors: 7 TM-spanning regions
- all aspects of physiology and pharmacology seconds

Tyrosine kinase linked receptors: e.g. insulin receptors

- metabolism, cell growth, cell reproduction minutes to hours

Intracellular receptors
Steroid receptors days
 adrenaline) G protein sitting near
receptor activates
enzyme (in this case)

eg heart in the
SA node, this
will change heart
rate as a result of
called G protein because binds second
guanosine triphosphate (GTP) messenger
and uses the energy from that to
bind to something else in the cell
membrane and produces a second
messenger

Fig. 11.12 Campbell et al. 2014

Fig. 11.14 Campbell et al. 2014
Gproteincoupledreceptors(GPCRs)
seven transmembrane spanning domains (7 TMDs)

the largest family of receptors:

>1000 members in human genome
150 orphans
>50% of current drugs target GPCRs

activated by a variety of stimuli:

light, ions (eg. Ca2+), odourants, gustative molecules,
neurotransmitters, hormones, peptides, proteins.

GPCRs interact with heterotrimeric G proteins to control the

activity of enzymes, ion channels, and intracellular
signal transduction pathways
 better representation of G protein receptors than the blob just now

Gproteincoupledreceptors(GPCRs)
Ligand
Ligands
Plasma
membrane

signals

GTP

3 different peptides, a gold, green and red one interacting with each other, that is the heterotrimeric part, G protein actually consists of 3
different proteins interacting with each other, goes on to stimulate something like adenylyl cyclase
Gproteincoupledreceptors(GPCRs)
Ligand
Effectors
Plasma
channels enzymes membrane

Plasma
membrane

Adenylyl cyclases
Phospholipases
Phosphodiesterases

Ca2+, K+ cAMP, cGMP,

IP3, DAG
GTP
(Second messengers)

must produce second messenger

 despite only a few receptors produced, a lot of cAMP, subsequent events amplified a lot, end
up with loads of products, so can get big response from just a few receptors stimulated

Amplificationofsignalling
Hormone ligand
Receptor
Adenylyl
Trimeric G proteins cyclase
(e.g. Gs)
GTP
cAMP GTP
PKA
cAMP cAMP
cAMP cAMP
PKA cAMP
Enzyme X cAMP
PKA PKA GTP
cAMP
cAMP cAMP cAMP
cAMP
cAMP PKAcAMP PKAcAMP
cAMP
cAMP cAMP
PKA cAMPPKA
cAMP cAMPcAMPcAMP cAMP
cAMP cAMP cAMPPKA PKA
cAMP cAMPPKA cAMP
cAMP cAMP cAMP
cAMP cAMP
cAMP

Product of
enzyme X
 Adenylyl cyclase turns ATP into cyclic AMP

ATP adenosine triphosphate cellular energy!!

cAMP is second messenger for quite a few different sort of receptors

Fig. 11.11 Campbell et al. 2012

 Receptortypes
Plasma Membrane Receptors
Ion channel receptors:
- Na+ channel opened by ligand e.g. nictoninc
receptors fast neurotransmission

G protein-coupled receptors: 7 TM-spanning regions

- all aspects of physiology and pharmacology

Tyrosine kinase linked receptors: e.g. insulin receptors

- metabolism, cell growth, cell reproduction

Intracellular receptors
Steroid receptors
 Howdoesinsulinwork??
How does insulin talk to the cell??
What does it interact with on the membrane?
That has to then tell the cell that insulin is present
and to do something about it

How???

works on insulin receptor that is much simpler than G protein coupled thing, one transmembrane
going through cell membrane, this family causes activation of a kinase

look at next slides, its a story :)

diagram incomplete, should be a gif
 Phosphorylation
Cascades
kinase causes phosphorylation

Mediated by enzymes
called KINASES
these transfer
phosphate and activate
or inactivate target proteins

Phosphate = PO4-
get loads of proteins getting phosphate added to them, which causes
something to happen inside the cell

Fig. 11.15 Campbell et al. 2014

 Proteinphosphorylation
OH

OH

CH2 CH-CH3 O
.NH-CH-CO. .NH-CH-CO.
O P O
Tyrosine (Y) Threonine (T)

OH Kinases + ATP O

CH2 CH2
Phosphatases
.NH-CH-CO. .NH-CH-CO.
Serine (S) Phosphoserine
phosphorylation will happen on tyrosine, threonine or serine bc they have OH
groups, they get phosphrylated, can change its shape, its interaction with other
proteins, might change the location of the protein
 Roleofproteinphosphorylation
P
Conformational
change
protein
P
P

P
Protein-protein
interactions

Change in cellular
location

These changes lead to activation or inactivation of the target proteins!

 Insulinreceptors:tyrosinekinase receptors
insulin binds two receptors together
insulin IRS1 = insulin
Insulin receptor substrate 1
just understand a lot of phosphates receptor
glucose IRS1
kinases
P P P
P
P
PI-3 kinase P

P inactive P
GS
GSK
glycogen P
GSK P

P Protein kinase B
GSK = glycogen synthase
kinase: inactivates
Glucose transporters glycogen synthase (GS)
moves to cell membrane, lets glucose into the cell, insulin gets released and as well as that it stores glucose as glycogen
 Receptortypes
Plasma Membrane Receptors
Ion channel receptors:
- Na+ channel opened by ligand e.g. nictoninc
receptors fast neurotransmission

G protein-coupled receptors: 7 TM-spanning regions

- all aspects of physiology and pharmacology

Tyrosine kinase linked receptors: e.g. insulin receptors

- metabolism, cell growth, cell reproduction

Intracellular receptors
Steroid receptors
 Steroidhormone
interactingwith
anintracellular
steroidreceptor

completely intracellular, go into nucleus, change expression of genes, very slow

Fig. 11.9 Campbell et al. 2014

 A/ProfLesleyLluka

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