Lecture 17: Intracellular Signaling

What are G-Proteins?

Guanine nucleotide binding proteins involved in transmitter signaling

What do receptors do to G-proteins?

Receptors catalyze the conversion of G Proteins into the active GTP bound state

What are the two-interconvertible states of G Proteins?

Active (GTP-bound)
Inactive (GDP-bound)

G-proteins are predominantly _

trimeric (comprised of three monomers)

What are the subunits of G-proteins and what do they do?

Alpha subunit: catalyzes the GTPase activity

Beta/gamma subunits: interacts with alpha subunit when bound to GDP

What are the characteristics of alpha-subunits of G-proteins?

sensitive to cholera and pertussis toxin

stimulate and inhibit adenylate cyclase

activate cGMP phophodiesterase and PLC

regulate Na-K exchange, PI3K (phosphatidylinositol 3-kinase)

What are the characteristics of beta/gamma subunits of G-proteins?

determine which receptors couple to G-Proteins

inhibit many adenylate cyclases (except type II and IV)

regulate stimulation of beta-isoform of PLC, K+ channels and PLA2

What are the subtypes of G Proteins?

Gs, Gi, Go, and tranducin

Which G protein subtypes are sensitive to cholera toxin?

Gs and transducin

Which G protein subtypes are sensitive to pentussis toxin?

Gi, Go, and transducin

What does cholera toxin also inhibit?

GTPase activity

What does ADP ribosylation of G Proteins involve?

ADP ribosylation involves transfer of ADP-ribose from NAD+ to arginine (by cholera toxin) or cysteine (by pertussis toxin)

What happens to signals originating from activate G protein receptors?

They can either converge or diverge

The response specificity of GPCR signaling determines what?

1. the degree of integration of signals
2. whether cell stimulation will produce a focused response to an NT or a coordination of divergent responses

G-Protein Signaling via adenylate cyclases (AC)

How many isoforms of adenylate cyclase are known?

11

G-Protein Signaling via adenylate cyclases (AC)

How are the levels of cAMP regulated

The levels of cAMP are highly regulated due to the balance between cAMP synthesis by cAMP and its degradation via phophodiesterases (PDEs)

What are the second messengers of G-Proteins?

cyclic AMP (cAMP)
Phospholipids
Calcium

How is the balance of cAMP maintained?

By the activities of adenylate cyclase and phosphodiesterase, respectively

G-Protein-based second messengers: Calcium

What roles does Calcium possess?

1. carrier of electrical current

2. acts as a second messenger

What mobilizes intracellular calcium?

Inositol triphosphase (IP3)

What mediates calcium-induced release from sarcoplasmic reticulum

Ryanodine receptors

What are Icrac channels?

calcium-release activated calcium channels

How are Icrac channels different from ryanodine receptors?

Icrac receptors are localized on plasma membrane near the endoplasmic reticulum