Insights into the mechanisms of membrane curvature and vesicle scission by the
small GTPase Sar1 in the early secretory pathway
#MMPMID25193674
Hariri H
; Bhattacharya N
; Johnson K
; Noble AJ
; Stagg SM
J Mol Biol
2014[Nov]; 426
(22
): 3811-3826
PMID25193674
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The small GTPase protein Sar1 is known to be involved in both the initiation of
COPII-coated vesicle formation and scission of the nascent vesicle from the
endoplasmic reticulum. The molecular details for the mechanism of membrane
remodeling by Sar1 remain unresolved. Here, we show that Sar1 transforms
synthetic liposomes into structures of different morphologies including tubules
and detached vesicles. We demonstrate that Sar1 alone is competent for vesicle
scission in a manner that depends on the concentration of Sar1 molecules
occupying the membrane. Sar1 molecules align on low-curvature membranes to form
an extended lattice. The continuity of this lattice breaks down as the curvature
locally increases. The smallest repeating unit constituting the ordered lattice
is a Sar1 dimer. The three-dimensional structure of the Sar1 lattice was
reconstructed by substituting spherical liposomes with galactoceramide lipid
tubules of homogeneous diameter. These data suggest that Sar1 dimerization is
responsible for the formation of constrictive membrane curvature. We propose a
model whereby Sar1 dimers assemble into ordered arrays to promote membrane
constriction and COPII-directed vesicle scission.
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