G Protein Trafficking - GPCR Signalling Complexes: Synthesis, Assembly, Trafficking and Specificity - page 198

Fig. 11.3 Model of activation-induced G protein trafficking . Upon GPCR-mediated activation
of an appropriate heterotrimeric G protein at the cytoplasmic surface of the PM, different, but not
necessarily mutually exclusive, pathways of reversible translocation have been described. One
series of studies has shown that after GPCR activation select Gb g can undergo rapid (within
seconds) movement from the PM to the Golgi. Then, Gb g can return from the Golgi to the PM
with similar rapidity. This cycle of Gb g movement has been described as diffusion-mediated.
Interestingly, the rapid activation-induced Gb g PM-Golgi cycle depends upon palmitoylation, and
likely by extension depalmitoylation. However, Gb g appears to undergo this cycle while Ga
remains on the PM; thus, Ga at the Golgi during activation-induced rapid translocation is indicated
by the question mark. In another pathway, GPCR-mediated activation promotes depalmitoylation
of Ga allowing Ga to translocate off of the PM. This pathway is slower (minutes) than the
PM-Golgi pathway. Gb g has also been observed to show such slower movement off of PM along
with Ga . G a may simply be released into the cytoplasm by virtue of its depalmitoylation, or it may
follow a vesicle-mediated pathway involving recycling endosomes together with Gb g. In this slower
pathway, Ga and Gb g would return to the PM even slower (0.5-1 h). The figure also indicates that
Ga and Gb g traffic independently of GPCR internalization. The models in this figure focus on
translocation of G proteins in non-visual systems. See the text and accompanying references for
more details regarding light-activated translocation of visual G proteins
heterotrimer is attached tightly to the membrane due to the presence of two lipids,
myristate and farnesyl. However, when light-activated rhodopsin promotes the loss of
GDP and binding of GTP by Ga t , G a t and Gb 1 g 1 dissociate and now each subunit is
able to translocate off the membrane due the weaker attachment by one lipid. Indeed,
it has been demonstrated that more than 80% of Ga t and Gb 1 g 1 are released from the
membrane within minutes of light activation, and this dramatic translocation has the
critical physiological role of allowing adaptation of the photoresponse to very bright
conditions (Sokolov et al. 2002 ) . After translocation off of rod outer segment