A Rab Effector Called the Exocyst and Related Vesicle Tether Complexes - Ras Superfamily Small G Proteins: Biology and Mechanisms 2 - page 74

4.9.1 Interactions with Rabs

Three of the four CATCHR complexes have been shown to act as direct effectors of
a Rab GTPase. In yeast the exocyst binds to Sec4-GTP through the Sec15p subunit
and this interaction is thought to help recruit the exocyst to secretory vesicles (Guo
et al. 1999b ), as described in an earlier section. In animal cells Sec15 interacts with
Rab11, a GTPase that controls export from recycling endosomes (Wu et al. 2005 ).
In both cases the exocyst is implicated in promoting the interaction of
Rab-associated vesicles with the plasma membrane in preparation for fusion. It is
not known if the Rab interaction has any role beyond recruitment of the exocyst,
although an unassembled pool of Sec3p was found to develop in a sec4-8 mutant
upon a shift to its restrictive temperature, suggesting a possible role for Sec4p in
exocyst assembly (Guo et al. 1999b ).
The COG complex interacts with Ypt1-GTP in yeast, while in mammalian cells
it interacts not only with the Ypt1 homologue, Rab1-GTP, but also a number of
other Golgi-localized Rab proteins (Miller et al. 2013 ). This interaction is needed
for the normal Golgi localization of COG. The GARP complex interacts with Rab6
(Liewen et al. 2005 ), or its yeast homologue Ypt6 (Siniossoglou and Pelham 2002 ),
through its Vps52 subunit. The Dsl1 complex is the only member of this group not
known to interact with a Rab protein. As in the case of the exocyst, these tethers are
recruited to specific membranes by their interactions with Rabs; however, addi-
tional roles for the Rabs in tether function have not been excluded.

4.9.2 Interactions with SNAREs

All four CATCHR complexes have been shown to interact with at least a subset of
the SNAREs that catalyze fusion of the tethered transport vesicle to the acceptor
compartment. Rather than list them all, I refer readers to a very recent review (Hong
and Lev 2014 ). These include interactions with both the SNAREs on transport
vesicles as well as SNAREs on the acceptor compartments. Furthermore, loss of
tether function leads to a failure to assemble the SNAREs into a fusion-competent,
four-helix bundle. However, this could potentially reflect either a direct role in
catalyzing SNARE complex assembly or an indirect role in bringing the vesicle into
sufficient proximity to the target compartment to permit SNARE complex assembly
at the intrinsic rate. To date the only direct, active role in SNARE complex
assembly has been shown for the Dsl1 complex. A modest acceleration of assembly
was shown in vitro using the soluble, cytoplasmic domains of the relevant SNAREs
(Ren et al. 2009 ).
An additional level of complexity arises from the observation that these tethers
interact not only with SNAREs, but also with other SNARE interacting proteins,
such as the Sec1/Munc18 family members that have themselves been implicated in
SNARE assembly (Laufman et al. 2009 ; Morgera et al. 2012 ). A more