CAENORHABDITIS-ELEGANS RAB-3 MUTANT SYNAPSES EXHIBIT IMPAIRED FUNCTION AND ARE PARTIALLY DEPLETED OF VESICLES

Rab molecules regulate vesicular trafficking in many different exocyti c and endocytic transport pathways in eukaryotic cells. In neurons, ra b3 has been proposed to play a crucial role in regulating synaptic ves icle release. To elucidate the role of rab3 in synaptic transmission, we isolated and characterized Caenorhabditis elegans rab-3 mutants. Si milar to the mouse rab3A mutants, these mutants survived and exhibited only mild behavioral abnormalities. In contrast to the mouse mutants, synaptic transmission was perturbed in these animals. Extracellular e lectrophysiological recordings revealed that synaptic transmission in the pharyngeal nervous system was impaired. Furthermore, rab-3 animals were resistant to the acetylcholinesterase inhibitor aldicarb, sugges ting that cholinergic transmission was generally depressed. Last, syna ptic vesicle populations were redistributed in rab-3 mutants. In motor neurons, vesicle populations at synapses were depleted to 40% of norm al levels, whereas in intersynaptic regions of the axon, vesicle popul ations were elevated. On the basis of the morphological defects at neu romuscular junctions, we postulate that RAB-3 may regulate recruitment of vesicles to the active zone or sequestration of vesicles near rele ase sites.