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10/14/19
1
Molecular and Cellular Biology
08.1. Cell Signalling I:
Signal Transduction and Short-TermCellular Responses
Prof. Dr. Klaus Heese
- G-protein signalling
Cell – Cell Communication Cell – Cell CommunicationNeuron-Neuron
or Neuron-Muscle
Synaptic Transmission
Neurotransmitters in the brain
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Ligand – Receptor interactionexperimental
Cell signalling
studies
e.g. pharmaceutical industry studies
G-Protein
Signalling
GTP/GDP
On / Off switch
Second Messengers in Cell Signalling
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PC = phosphatidylcholine; PE = phosphatidylethanol; PS = phosphatidylserine; SM = sphingomyelin; PI = phosphoinositol
Molecules of a
Biomembrane
Fatty Acids & Lipids G-Protein-Coupled Receptor - 7-TransMembrane-Receptors
a 7TM-GPCR
G-protein-
coupled Receptor
7-TM-Rs
Hormone /G-Protein-Coupled Receptor Signalling
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Ligand
In-Vitro Fluorescence-activated live-Cell Imaging Analysis of G-Protein-Coupled Receptor Signalling Ligand
ligand
7TM-GPCR
G-protein
Effector
2nd messenger
activated target(change in membrane potential and ion-gradient)
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Rhodopsin
Signalling
in a human
Rod Cell
(eye/vision)
(conformation change)
Rhodopsin consists of the protein moiety
opsin and a reversibly
covalently bound cofactor, retinal.
PDE:cGMP PhosphoDiEsterase
ligand
7TM-GPCR(Rhodopsin =(opsin+retinal)
G-protein
Effector
2nd messenger
activated target:Ion channel
---> 3rd messenger --->(change in membrane potential and ion-gradients)
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effector protein/enzyme
(secondmessenger)
Different Ligand/Receptor systems may modulate/act on the same Effector
activated target: e.g. PKA
effector-
protein/enzyme
Signalling
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cAMP-PKA Signalling
& Cell Metabolism
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Signal Amplification
cAMP-PKA-PDE control cycle GPCR – Ca2+ Signalling
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321
IP3 quickly diffuses throughthe cytosol and binds to an IP3–gated calcium channel in the ERmembrane, causing it to open.
4 The calcium ionsactivate the nextprotein in one or moresignaling pathways.
6Calcium ions flow out ofthe ER (down their con-centration gradient), raisingthe Ca2+ level in the cytosol.
5
DAG functions asa second messengerin other pathways.
Phospholipase C cleaves aplasma membrane phospholipidcalled PIP2 into DAG and IP3.
A signal molecule bindsto a receptor, leading toactivation of phospholipase C.
EXTRA-CELLULARFLUID
Signal molecule(first messenger)
G protein
G-protein-linkedreceptor
Variousproteinsactivated
Endoplasmicreticulum (ER)
Phospholipase CPIP2
IP3(second messenger)
DAG
Cellularresponse
GTP
Ca2+
(second messenger)
Ca2+
IP3-gatedcalcium channel
Calcium Signalling(diacylglycerol)
GPCR – Ca2+ Signalling
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Example
2nd messenger