Rabx-5 regulates RAB-5 early endosomal compartments and synaptic vesicles in C. elegans.
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.
Neurobiology Section, Division of Biological Sciences, University of California San Diego, La Jolla, California, United States of America. ssann@ucsd.edu
Sharon B
SB
Sann
Matthew M
MM
Crane
Hang
H
Lu
Yishi
Y
Jin
D000375:Aging / Q000378:metabolism; D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002451:Cell Compartmentation; D004705:Endocytosis; D011992:Endosomes / Q000378:metabolism*; D059330:GABAergic Neurons / Q000166:cytology / Q000378:metabolism; D017238:Genes, Helminth / Q000235:genetics; D020662:Guanine Nucleotide Exchange Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D009046:Motor Neurons / Q000166:cytology / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D010641:Phenotype; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013572:Synaptic Vesicles / Q000378:metabolism*; D033921:Vesicular Transport Proteins / Q000378:metabolism*
D029742:Caenorhabditis elegans Proteins; D020662:Guanine Nucleotide Exchange Factors; C575474:RABX-5 protein, C elegans; C558452:Rab-5 protein, C elegans; D011993:Recombinant Fusion Proteins; D033921:Vesicular Transport Proteins