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Early endosomal membrane compartments are required for the formation and recycling of synaptic vesicles, but how these compartments are regulated is incompletely understood. We performed a forward genetic screen in  C. elegans  for mutations that affect RAB-5 labeled early endosomal compartments in GABAergic motoneurons. Here we report the isolation and characterization of one mutation,  rabx-5 . The  rabx-5  mutation leads to decreased intensity of YFP::RAB-5 in the cell soma but increased intensity in the synaptic and intersynaptic regions of the axon. This effect is due to the bias of the cycling state of RAB-5, and results from a change in the organization of the early endosomal compartment as well as the membrane binding state of RAB-5. Synaptic vesicle accumulation is altered in  rabx-5  mutants, and synaptic transmission from cholinergic neurons is decreased. Early endosomal membrane compartments show disorganization with ageing and  rabx-5  mutant animals age faster. These results suggest that  rabx-5  regulation of RAB-5 compartments is important for maintaining proper synaptic function throughout the lifetime.

Rabx-5 Regulates RAB-5 Early Endosomal Compartments and Synaptic Vesicles in C. elegans