Loss of the Sec1/Munc18 family proteins VPS-33.2 and VPS-33.1 bypass a block in endosome maturation in C. elegans

The end of the life of a transport vesicle requires a complex series of tethering, docking and fusion events. Tethering complexes play a crucial role in the recognition of membrane entities and bringing them in close opposition, thereby coordinating and controlling cellular trafficking events. Here we provide a comprehensive RNAi analysis of the CORVET and HOPS tethering complexes in metazoans. Knockdown of CORVET components promoted RAB-7 recruitment to subapical membranes, while in HOPS knockdowns RAB-5 was found also on membrane structures close to the cell center, indicating the RAB conversion might be impaired in the absence of these tethering complexes. Unlike in yeast, metazoans have two VPS33 homologues, which are Sec1/Munc18 family proteins involved in the regulation of membrane fusion. We assume that in wild type, each tethering complex contains a specific SM protein but that they may be able to substitute for each other in case of absence of the other. Importantly, knockdown of both SM proteins allowed the bypass of the endosome maturation block in sand-1 mutants. We propose a model in which the SM proteins in tethering complexes are required for the coordinated flux of material through the endosomal system.