Caenorhabditis elegans wsp-1 regulation of synaptic function at the neuromuscular junction.
The Rho GTPase members and their effector proteins, such as the Wiskott-Aldrich syndrome protein (WASP), play critical roles in regulating actin dynamics that affect cell motility, endocytosis, cell division, and transport. It is well established that Caenorhabditis elegans wsp-1 plays an essential role in embryonic development. We were interested in the role of the C. elegans protein WSP-1 in the adult nematode. In this report, we show that a deletion mutant of wsp-1 exhibits a strong sensitivity to the neuromuscular inhibitor aldicarb. Transgenic rescue experiments demonstrated that neuronal expression of WSP-1 rescued this phenotype and that it required a functional WSP-1 Cdc42/Rac interactive binding domain. WSP-1-GFP fusion protein was found localized presynaptically, immediately adjacent to the synaptic protein RAB-3. Strong genetic interactions with wsp-1 and other genes involved in different stages of synaptic transmission were observed as the wsp-1(gm324) mutation suppresses the aldicarb resistance seen in unc-13(e51), unc-11(e47), and snt-1 (md290) mutants. These results provide genetic and pharmacological evidence that WSP-1 plays an essential role to stabilize the actin cytoskeleton at the neuronal active zone of the neuromuscular junction to restrain synaptic vesicle release.
Zhang
Yuqian
Y
Department of Biology, York University, Toronto, Ontario M3J 1P3, Canada.
Kubiseski
Terrance J
TJ
D000199:Actins / Q000378:metabolism; D000448:Aldicarb / Q000633:toxicity; D000818:Animals; D017173:Caenorhabditis elegans / Q000166:cytology* / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D003599:Cytoskeleton / Q000187:drug effects / Q000378:metabolism; D004252:DNA Mutational Analysis; D007700:Kinetics; D009154:Mutation; D009469:Neuromuscular Junction / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009928:Organ Specificity; D010243:Paralysis / Q000139:chemically induced; D010641:Phenotype; D017434:Protein Structure, Tertiary; D009435:Synaptic Transmission / Q000187:drug effects; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism
D000199:Actins; D029742:Caenorhabditis elegans Proteins; C532812:wsp-1 protein, C elegans; D000448:Aldicarb; D020764:cdc42 GTP-Binding Protein