Identification of the switch in early-to-late endosome transition.
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.
Poteryaev
Dmitry
D
Biozentrum, University of Basel, Klingelbergstrasse 70, Basel 4056, Switzerland.
Datta
Sunando
S
Ackema
Karin
K
Zerial
Marino
M
Spang
Anne
A
D000818:Animals; D030801:Animals, Genetically Modified; D017173:Caenorhabditis elegans / Q000166:cytology / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism; D011992:Endosomes / Q000378:metabolism*; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism; D010716:Phosphatidylinositols / Q000378:metabolism; D020691:rab GTP-Binding Proteins / Q000378:metabolism; D020696:rab5 GTP-Binding Proteins / Q000378:metabolism; D000090802:rab7 GTP-Binding Proteins
D029742:Caenorhabditis elegans Proteins; D020662:Guanine Nucleotide Exchange Factors; D010716:Phosphatidylinositols; C506114:SAND-1 protein, C elegans; C118303:phosphoinositide-3,4,5-triphosphate; D000090802:rab7 GTP-Binding Proteins; D020691:rab GTP-Binding Proteins; D020696:rab5 GTP-Binding Proteins