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fission to produce coated vesicles and this process is suppressed by activa-
tion of G
i/o
.
A number of small ras-related GTP-binding proteins of the rab-family,
is also found in association with the vesicle transport machinery and are
believed to serve crucial roles in vesicle formation, transport, and fusion
with target membranes (Novick and Zerial, 1997; Rothman and Söllner,
1997; Chavrier
et al.,
1990a,b). In mammalian cells rab1a and rab1b have
been shown to be essential in the early steps of vesicle transport. This is in
line with the proposed function of the rab1-related yeast ypt1 and sec4 pro-
teins which appear to be important factors in subsequent targeting and
fusion of transport vesicles (Segev, 1991; Walworth, 1989; Goud
et al.,
1988).
Rab1a can, when overexpressed, replace Ypt1p function in yeast (Haubruck
et
al.,
1989). Rab1b is located in the ER and in the Golgi apparatus
and is required for ER to Golgi transport as well as intra-Golgi transport
(Plutner
et al.,
1991). This function may be due to the association of
rab1 to transport vesicles (Schwaninger
et al.,
1992). Of particular interest
is the finding that the ypt1 protein is palmitoylated on at least one of
the two cysteines in its C-terminus. The acylation seems to determine
the degree of membrane association since the modified protein predomi-
nantly resides in the membrane fraction while a ypt1 protein lacking the
C-terminal residues is exclusively found in the soluble fraction (Molenaar
et al.,
1988). Since the C-terminal domain of rab proteins have been sug-
gested to act as targeting signals and is highly conserved (Chavrier
et al.,
1991a; Molenaar
et al.,
1988) there is reason to believe that the mem-
brane association and function of rab1, at least in part, also depends on
palmitoylation.
It is intriguing that the effects of G-protein modulators parallels the
acylation of p62. These observations suggest the regulation of a protein acyl-
transferase involved in vesicle assembly and membrane budding by a he-
terotrimeric G-protein. Dynamic palmitoylation also plays an important
role in cycling of heterotrimeric G-proteins between basal and agonist-
activated states (reviewed in Mumby, 1997). Palmitoylation of
α
α
s
has been
shown to increase the affinity for
βγ
(Iiri
et al.,
1996), and when bound to
βγ
palmitoylated
α
is
more
resistant
to
depalmitoylation
by
a
protein
s
thioesterase (Iiri
et al.,
1996). Likewise,
βγ
stimulates palmitoylation of
α
s
and
11
(Dunphy
et al.,
1996). The current model predicts that prior to acti-
vation G
α
is palmitoylated, but during activation it becomes deacylated and
dissociates from
α
to modulate the activity of its downstream effectors.
GTP-hydrolysis triggers G
βγ
is then reacylated
and inactivated (Mumby, 1997). Thus, in this regulatory scheme ARF, COPs,
heterotrimeric G-proteins and rab proteins operating together with specific
palmitoyl transferases may be important factors regulating the process of
assembling of and pinching off vesicles.
α
to reassociate with
βγ,
G
α
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