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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.

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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