Cell signaling

Part II

Sit back, relax, and enjoy the show.

Role of G-protein in CellularSignaling

GS GiGq

G12

Na+ channels

Ca2+ channels

cAMP K+ channels

cAMP

PLC, cGMP

PLC-1-3

Biological Function- Smell &Taste (~1000 receptors)- light- Neurotransmitters- Chemotoxin- Exocytosis- Blood pressure- Embryogenesis- cell growth & differentiation- HIV infection- Oncogenesis

Na+/K+ exchangeregulation

- Ion channels- PI3K- PLC-- adenylyl cyclases

Effectors of

The activated receptorhas GEF activityG nucleotide Exchange Factor

Galpha-GTP is active and can Act on effectors

The intrinsic GTPase activityreturns the G protein complexto its resting state.

Hormone activation and inhibition of adenyl cyclase is mediated by Gs and Gi

Cholera toxinknocks out theGTPase activity so thatthere is constant ACstimulation. This opens channels to permitwater flow into theintestine

Pertusis toxin (WhoppingCough) blocks the GDP of Gi so that there is no inhibition of AC.

Vibrio choleraBordetella perusis

B does it too

So what?

What can G-protein-coupled signaling do?

3 neurons talking

Modulatory synapse

PKA, for those who want to know

Glutamate is also a neurotransmitter

Serotonin is your friend Wow man, that’s the real stuff

Now for something completely different: vision.Well, not really that different.

How is light absorbed?How is the signal transduced?How do rod cells adapt to large variations in light intensity?

Direction of light into your eye

800 eyes, ommatidia22 cells each8 neurons, retinula, R cells

RTK, SevenlessBOSS, Bride of Sevenless

Constitutively active Rasrescues

Activation means recruitment

Proximity = action