A Rab Effector Called the Exocyst and Related Vesicle Tether Complexes - Ras Superfamily Small G Proteins: Biology and Mechanisms 2 - page 66

Chapter 4
A Rab Effector Called the Exocyst
and Related Vesicle Tether Complexes
Peter Jay Novick
Abstract Vesicular transport between membrane-bounded organelles requires, in
most cases, a large multi-subunit protein complex that serves in the initial recog-
nition of the target compartment by the vesicle, a step commonly termed tethering.
Four different tethers that act at four different stages of membrane traffic exhibit a
common architecture: at least some of their subunits form rod-shaped structures
from helical bundles that are stacked in series. These subunits are often linked to
each other through coiled-coil domains at their amino termini to form a multi-
armed complex. In three cases these tethers are recruited to the membrane by
binding to the activated form of a Rab GTPase and in two cases interactions with
vesicle coat proteins are thought to play a role in vesicle recognition. Interactions
with SNARE proteins on both the vesicle and target membranes suggest possible
roles in directing SNARE complex assembly in preparation for membrane fusion.
Here, we will review in depth the first of these tethers, the exocyst complex that is
required for the exocytic fusion of vesicles with the plasma membrane, and then
discuss various parallels in both structure and function with the related tethers,
COG, GARP, and Dsl, that act on other transport pathways.
Keywords Rab effector • Vesicle tether
4.1 Backstory of the Exocyst
Most subunits of the exocyst were first identified in a genetic screen for
temperature-sensitive (ts) yeast secretory ( sec ) mutants blocked in general protein
secretion (Novick et al. 1980 ). Of the ten sec complementation groups blocked at
the post-Golgi stage of the secretory pathway, six were ultimately shown to be