Question

How does G⍺ stay associated with the plasma membrane after release from GPCR?

1. Lipid rafts.
2. G⍺ is phosphorylated.
3. G⍺ is farnesylated.
4. G⍺ is palmitoylated.
5. G⍺ is covalent bound to positive charge of phospholipids.
6. G⍺ contains a transmembrane domain that is enriched for hydrophobic residues.

Why is it important that G⍺ stay associated with the plasma membrane after release from GPCR?

1. It isn’t, in fact this is one way to prevent “runaway signaling” (i.e. how G⍺ acts as a molecular timer) following epinephrine binding to the receptor (i.e. by allowing G⍺ to diffuse into the cytoplasm where it can no longer interact with GPCR’s and initiate subsequent signaling events).  The signal remains off until more G⍺ protein is synthesized.
2. Following release, G⍺ must interact with another integral membrane protein, effector proteins (ex: adenylyl cyclase).
3. This allows G⍺ to be reused; after hydrolyzing GTP -> GDP, G⍺ can re-associate with Gβ,G?, GPCR and initiate subsequent signals without the cell having to synthesize more G⍺ protein.
4. G⍺ is required for endocytosis of GPCR’s leading to receptor-down-regulation, which occurs at the plasma membrane and leads to desensitization of the signal.

Answer 1

1. The correct answer will be (d)G⍺ is palmitoylated.

Heterotrimeric G proteins undergo co/post-translational modifications in the alpha (myristic and/or palmitic acid) and the gamma (farnesol or geranylgeraniol) subunits. These modifications not only assist the G protein to localize to the membrane but they also help distribute the heterotrimer (Gαβγ) and the subunits generated upon activation (Gα and Gβγ) to appropriate membrane microdomains.

2. The correct answer will be

(c)This allows G⍺ to be reused; after hydrolyzing GTP -> GDP, G⍺ can re-associate with Gβ,G?, GPCR and initiate subsequent signals without the cell having to synthesize more G⍺ protein.