1. Cell to Cell Communication via G-Protein Linked Receptors
Monday, November 12, 2018
Cell to Cell Communication via G-Protein Linked Receptors
Packet #22
Chapter #11

2. Introduction I
Monday, November 12, 2018Monday, November 12, 2018
G-protein-linked receptors, and enzyme-linked receptors, are used by practically every cell type of the body
G-protein linked receptors form the largest family of cell-surface receptors
Mediate responses to an enormous diversity of extracellular signal molecules

3. Introduction II Theory of Evolution Connection
Monday, November 12, 2018Monday, November 12, 2018
“Evolutionary” origins are very “ancient.”
G-protein linked receptors are found in eukaryotic cells such as yeasts but are not found in bacteria even though there are “similar” membrane proteins (bacteriorhodopsin).

4. Introduction III Structure of G-Protein
Monday, November 12, 2018Monday, November 12, 2018
G proteins are composed of three subunits α β γ
The α subunit has GDP bound to it when the G-protein is inactive.
When signal binds to G-protein linked receptor, the α subunit ejects GDP and puts in GTP.

5. Introduction IV Active to Inactive G-Protein
Monday, November 12, 2018Monday, November 12, 2018
When active with GTP bound, The G protein breaks up into the α subunit and the βγ complex.
α subunit has within an intrinsic GTPase.
Which, after a certain time hydrolyzes GTP to GDP
α subunit reassociates itself with the βγ complex and the signal is shut off.

6. Introduction V
Monday, November 12, 2018Monday, November 12, 2018
Once activated by ligand, G-proteins initiate a series of reactions that ultimately result in a specific intracellular response
Active receptor can activate many effector molecules.
Muscle?

7. G Protein Linked Receptors
Monday, November 12, 2018Monday, November 12, 2018

8. G-Proteins & Ion Gated Channels
Monday, November 12, 2018
G-Proteins & Ion Gated Channels

9. Introduction I
Monday, November 12, 2018Monday, November 12, 2018
The target for the G-protein subunits (α subunit) are either ion channels or membrane-bound enzymes (Packet #23}

10. Examples of G-Proteins linked to Ion Channels
Monday, November 12, 2018Monday, November 12, 2018
Heart
Nerve fibers, that tell the muscle cells to reduce contraction, slowing the heartbeat, do so by releasing acetylcholine.
Acetylcholine binds to G-protein linked receptor on muscle cells.
G-protein is activated and the βγ complex binds to the K+ channels in the membrane of the heart muscle cell plasma membrane.
K+ channel opens.
Electrochemical gradient is altered.
Muscle cell contracts less frequently.

11. G-Proteins & Membrane-Bound Enzymes
Monday, November 12, 2018
G-Proteins & Membrane-Bound Enzymes

12. G-Protein & Membrane Enzymes
Monday, November 12, 2018Monday, November 12, 2018
G-protein interactions with enzymes have more complex circumstances.
The most frequent target enzyme is
Adenylate cylase
Adenylate Cyclase helps produce
cAMP
Phospholipase C
Enzyme that produces
Inositol triphosphate
Diacyglycerol

13. G-Proteins & Secondary Messengers
Monday, November 12, 2018
G-Proteins & Secondary Messengers

14. Introduction
Monday, November 12, 2018Monday, November 12, 2018
Small intracellular signaling molecules, in pathways where the extracellular signal is the first messenger, are called secondary messengers.
Examples
cAMP
IP3 (Inositol Triphosphate )
Diacylglycerol
Ca2+

15. Secondary Messenger Molecules Systems
Monday, November 12, 2018Monday, November 12, 2018
The two mostly recognized second messenger systems are
Adenylate cyclase system
Involves the use of G-proteins
See how rods are turned off in response to light
Calcium/phosphatidylinositol system

16. Second Messenger Molecules
Monday, November 12, 2018Monday, November 12, 2018
G Proteins activate second messengers
Are small, nonprotein, water-soluble molecules or ions
Intervene between original message and the ultimate effect of the cell
Part of the cascade of events that translate binding hormone, or neurotransmitter, into a cellular response
Two mostly recognized second messenger systems
Adenylate cyclase system
Calcium/phosphatidylinositol system

17. Adenylate Cyclase System cAMP Second Messenger
Monday, November 12, 2018Monday, November 12, 2018

18. Cyclic Adenosine Monophosphate (cAMP)
Monday, November 12, 2018Monday, November 12, 2018

19. Calcium ions and Inositol Triphosphate (IP3)
Monday, November 12, 2018Monday, November 12, 2018
Calcium, when released into the cytosol of a cell is an important second messenger in many different pathways.

20. Calcium ions and Inositol Triphosphate (IP3) II
Monday, November 12, 2018Monday, November 12, 2018
Calcium, found in the cytosol, is regulated by the cell itself.

21. G Proteins, Calcium ions and Inositol Triphosphate (IP3) I
Monday, November 12, 2018Monday, November 12, 2018
Phospholipase C acts on a membrane inositol phospholipid
A phospholipid with the sugar inositol attached to it.
Pathway begun by phospholipase C is called the inositol phospholipid pathway.
Phospholipase C generates two different messenger molecules.
Hydrophilic head of phospholipid is detached from the inositol phospholipid to produce inositol 1, 4, 5-triphosphate (IP3) while leaving the lipid diacylglycerol (DAG) tail embedded in the plasma membrane.
Both molecules play a crucial part in signaling inside the cell.
DAG helps activate protein kinase C and sets off a different set of intracellular processes.

22. Monday, November 12, 2018Monday, November 12, 2018