Journal of Cell Science 116, e1302 (2003)
Copyright © 2003 The Company of Biologists Limited
Rab4 and vesicle fission
During receptor-mediated endocytosis, ligand-bound receptors are
internalized into clathrin-coated endocytic vesicles; these are then rapidly
uncoated, before undergoing a series of fission events that segregate the
ligand (which is destined for degradation) from the receptor (which is
recycled). Clathrin uncoating is relatively well understood, but we know much
less about the fission process. Alan Wolkoff and co-workers have therefore
screened for proteins that might control fission, using an in vitro system
that reconstitutes microtubule-based motility and fission of early endocytic
vesicles containing the ligand asialoorosomucoid (see
p. 2749). They find that the
small GTPase Rab4 and the kinesin motor KIF2C are associated with
ligand-containing vesicles. Furthermore, they show that addition of
GST-conjugated Rab4-GTP inhibits motility and vesicle fission; preincubation
with the non-hydrolysable GTP analogue GTP-
-S has a similar effect.
GDP, by contrast, increases the extent of vesicle trafficking and fission. The
authors conclude that Rab4 serves as a molecular switch in endocytic vesicle
fission. They propose that hydrolysis of GTP bound to Rab4 triggers
kinesin-driven movement of the vesicles along microtubules, which results in
vesicle fission and consequently ligand/receptor segregation.
Related articles in JCS:
- Regulation of early endocytic vesicle motility and fission in a reconstituted system
- Eustratios Bananis, John W. Murray, Richard J. Stockert, Peter Satir, and Allan W. Wolkoff
JCS 2003 116: 2749-2761.
[Abstract]
[Full Text]
