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Identification of the Switch in Early-to-Late Endosome Transition
April 2010
April 2010
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Abstract
Sequential transport from early to late endosomes requires the coordinated activities
of the small GTPases Rab5 and Rab7. The transition between early and late endosomes
could be mediated either through transport carriers or by Rab conversion, a process
in which the loss of Rab5 from an endosome occurs concomitantly to the acquisition
of Rab7. We demonstrate that Rab conversion is the mechanism by which proteins pass
from early to late endosomes in Caenorhabditis elegans coelomocytes. Moreover, we
identified SAND-1/Mon1 as the critical switch for Rab conversion in metazoa. SAND-1
serves a dual role in this process. First, it interrupts the positive feedback loop
of RAB-5 activation by displacing RABX-5 from endosomal membranes; second, it times
the recruitment of RAB-7, probably through interaction with the HOPS complex to the
same membranes. SAND-1/Mon1 thus acts as a switch by controlling the localization
of RAB-5 and RAB-7 GEFs.
2010 Elsevier Inc. All rights reserved.