G Protein Trafficking - GPCR Signalling Complexes: Synthesis, Assembly, Trafficking and Specificity - page 200

charged membrane (Kosloff et al. 2008 ) . Accordingly, once G a t is dissociated from
Gb 1 g 1 , the electrostatic repulsion would promote Ga t translocation. Additionally,
the protein UNC119 was recently identified as a binding partner, with the exciting
finding that UNC119 binds to the acylated N-terminus of Ga t in a complex in which
the lipid is buried in a hydrophobic cavity of UNC119 (Zhang et al. 2011 ) . The
interaction of UNC119 with Ga t appears to promote the return of Ga t to outer seg-
ments (Zhang et al. 2011 ; Gopalakrishna et al. 2011 ) . Another mechanistic detail
that has been extensively addressed is the question of whether transducin transloca-
tion is driven by active transport or solely by diffusion. This has been a question of
much debate and controversy in the field. Although some reports indicate that
cytoskeletal elements are involved in transducin translocation and would thus serve
as tracks for motor-driven active transport (Peterson et al. 2005 ) , a number of
researchers argue for diffusion-mediated transport, based a great deal on theoretical
considerations (see these reviews for a in-depth discussion of mechanisms of trans-
ducin translocation, including diffusion versus active transport (Slepak and Hurley
2008 ; Artemyev 2008 ; Calvert et al. 2006 )). Although some of the underlying
mechanisms still need to be resolved, light-activated and reversible translocation of
transducin clearly provides our most detailed and robust example of activation-
induced trafficking of G proteins.
The Drosophila visual system has also been used as a model system to study
G protein trafficking. Of particular interest, the visual system in flies uses palmitoy-
lated Ga q to signal responses to light rather than the non-palmitoylated Ga t as is
used in vertebrate visual signaling. Nonetheless, Ga q has been shown to translocate
from membranes to the cytoplasm in response to light activation of photoreceptor
cells (Kosloff et al. 2003 ; Cronin et al. 2004 ; Frechter et al. 2007 ) . Similar to trans-
ducin in vertebrate visual signaling, Ga q translocation occurred in a matter of
minutes after light activation. On the other hand, in Drosophila visual signaling it
is not clear whether the relevant Gb g traffics from the membrane after light activa-
tion, although studies using flies with reduced levels of Gb g in the eye showed that
Ga q needs Gb g to return to the membrane. Furthermore, the recycling of Ga q
required the photoreceptor-specific myosin III NINAC (Cronin et al. 2004 ) .
Although this study suggests that active transport would thus drive Ga q back to the
membrane after light activation, more studies are needed to address the mechanism.
Lastly, and again similar to vertebrate signaling, changes in the membrane content
of Ga q allow adaptation to varying levels of light (Frechter et al. 2007 ) . Thus, light-
dependent translocation of G proteins appears to be a conserved mechanism for
light adaptation.
Activation-induced G protein translocation has also been clearly identified to
occur in non-visual signaling. Studies on Ga s provide the most information regard-
ing activation-induced trafficking of G proteins in non-visual systems. A number of
reports have demonstrated that Ga s can translocate from the PM to intracellular
locations upon activation by a GPCR, such as the b 2 -adrenergic receptor (b 2 -AR),
by cholera toxin or by introduction of a GTPase-inhibiting mutation (Allen et al.
2005 ; Ransnäs et al. 1989 ; Levis and Bourne 1992 ; Thiyagarajan et al. 2002 ;
Wedegaertner and Bourne 1994 ; Wedegaertner et al. 1996 ; Yu and Rasenick 2002 ;