RRC ID 46414
Author Mullen GP, Grundahl KM, Gu M, Watanabe S, Hobson RJ, Crowell JA, McManus JR, Mathews EA, Jorgensen EM, Rand JB.
Title UNC-41/stonin functions with AP2 to recycle synaptic vesicles in Caenorhabditis elegans.
Journal PLoS One
Abstract The recycling of synaptic vesicles requires the recovery of vesicle proteins and membrane. Members of the stonin protein family (Drosophila Stoned B, mammalian stonin 2) have been shown to link the synaptic vesicle protein synaptotagmin to the endocytic machinery. Here we characterize the unc-41 gene, which encodes the stonin ortholog in the nematode Caenorhabditis elegans. Transgenic expression of Drosophila stonedB rescues unc-41 mutant phenotypes, demonstrating that UNC-41 is a bona fide member of the stonin family. In unc-41 mutants, synaptotagmin is present in axons, but is mislocalized and diffuse. In contrast, UNC-41 is localized normally in synaptotagmin mutants, demonstrating a unidirectional relationship for localization. The phenotype of snt-1 unc-41 double mutants is stronger than snt-1 mutants, suggesting that UNC-41 may have additional, synaptotagmin-independent functions. We also show that unc-41 mutants have defects in synaptic vesicle membrane endocytosis, including a ∼50% reduction of vesicles in both acetylcholine and GABA motor neurons. These endocytic defects are similar to those observed in apm-2 mutants, which lack the µ2 subunit of the AP2 adaptor complex. However, no further reduction in synaptic vesicles was observed in unc-41 apm-2 double mutants, suggesting that UNC-41 acts in the same endocytic pathway as µ2 adaptin.
Volume 7(7)
Pages e40095
Published 2012-1-1
DOI 10.1371/journal.pone.0040095
PII PONE-D-12-06679
PMID 22808098
PMC PMC3393740
MeSH Adaptor Protein Complex 2 / metabolism* Adaptor Proteins, Vesicular Transport / genetics Adaptor Proteins, Vesicular Transport / metabolism* Animals Animals, Genetically Modified Caenorhabditis elegans / genetics Caenorhabditis elegans / metabolism Caenorhabditis elegans / ultrastructure Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* Carrier Proteins / metabolism Cloning, Molecular Drosophila Proteins / metabolism Endocytosis* Gene Expression Regulation Genes, Helminth / genetics Genome / genetics Mutation / genetics Nerve Tissue Proteins / metabolism Nervous System / metabolism Phenotype Protein Transport Synaptic Vesicles / metabolism* Synaptic Vesicles / ultrastructure Synaptotagmins / metabolism Vesicular Transport Proteins
IF 2.74
Times Cited 18
C.elegans tm1711 tm2426 tm3686