BIOL 2021 Lecture Notes - Lecture 9: Lipid-Anchored Protein, Gtpase, Cytosol

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o To ensure an orderly flow of vesicle traffic, transport vesicles must be
highly accurate in recognizing the correct target membrane with which to
fuse. process occurs in two steps. First, Rab proteins and Rab effectors
direct the vesicle to specific spots on the correct target membrane.
Second, SNARE proteins and SNARE regulators mediate the fusion of the
lipid bilayers. Rab proteins play a central part in the specificity of vesicle
transport. Like the coat-recruitment GTPases discussed earlier. the Rab
subfamily is the largest of the monomeric GTPase subfamilies. Their
highly selective distribution on these membrane systems makes Rab
proteins ideal molecular markers for identifying each membrane type
and guiding vesicle traffic between them. Rab proteins can function on
transport vesicles, on target membranes, or both. In their GDP-bound
state, they are inactive and bound to another protein (Rab-GDP
dissociation inhibitor, or GDI) that keeps them soluble in the cytosol; in
their GTP-bound state, they are active and tightly associated with the
membrane of an organelle or transport vesicle. Membrane-bound Rab-
GEFs activate Rab proteins on both transport vesicle and target
membranes. Once in the GTP-bound state and membrane-bound through
a now-exposed lipid anchor, Rab proteins bind to other proteins, called
Rab effectors. Rab effector proteins interact with active Rab proteins
located on the target membrane, vesicle membrane, or both, to establish
the first connection between the two membranes that are going to fuse. In
the example shown here, the Rab effector is a filamentous tethering
protein. Next, SNARE proteins on the two membranes pair, docking the
vesicle to the target membrane and catalyzing the fusion of the two
apposed lipid bilayers. During docking and fusion, a Rab-GAP (not shown)
induces the Rab protein to hydrolyze its bound GTP to GDP, causing the
Rab to dissociate from the membrane and return to the cytosol as Rab-
GDP, where it is bound by a GDP protein that keeps the Rab soluble and
inactive.
Fig 13-20 Dissociation of SNARES
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Document Summary

To ensure an orderly flow of vesicle traffic, transport vesicles must be highly accurate in recognizing the correct target membrane with which to fuse. process occurs in two steps. First, rab proteins and rab effectors direct the vesicle to specific spots on the correct target membrane. Second, snare proteins and snare regulators mediate the fusion of the lipid bilayers. Rab proteins play a central part in the specificity of vesicle transport. Like the coat-recruitment gtpases discussed earlier. the rab subfamily is the largest of the monomeric gtpase subfamilies. Their highly selective distribution on these membrane systems makes rab proteins ideal molecular markers for identifying each membrane type and guiding vesicle traffic between them. Rab proteins can function on transport vesicles, on target membranes, or both. Gefs activate rab proteins on both transport vesicle and target membranes. Once in the gtp-bound state and membrane-bound through a now-exposed lipid anchor, rab proteins bind to other proteins, called.

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