RRC ID 46412
著者 Monteiro MI, Ahlawat S, Kowalski JR, Malkin E, Koushika SP, Juo P.
タイトル The kinesin-3 family motor KLP-4 regulates anterograde trafficking of GLR-1 glutamate receptors in the ventral nerve cord of Caenorhabditis elegans.
ジャーナル Mol Biol Cell
Abstract The transport of glutamate receptors from the cell body to synapses is essential during neuronal development and may contribute to the regulation of synaptic strength in the mature nervous system. We previously showed that cyclin-dependent kinase-5 (CDK-5) positively regulates the abundance of GLR-1 glutamate receptors at synapses in the ventral nerve cord (VNC) of Caenorhabditis elegans. Here we identify a kinesin-3 family motor klp-4/KIF13 in a cdk-5 suppressor screen for genes that regulate GLR-1 trafficking. klp-4 mutants have decreased abundance of GLR-1 in the VNC. Genetic analysis of klp-4 and the clathrin adaptin unc-11/AP180 suggests that klp-4 functions before endocytosis in the ventral cord. Time-lapse microscopy indicates that klp-4 mutants exhibit decreased anterograde flux of GLR-1. Genetic analysis of cdk-5 and klp-4 suggests that they function in the same pathway to regulate GLR-1 in the VNC. Interestingly, GLR-1 accumulates in cell bodies of cdk-5 but not klp-4 mutants. However, GLR-1 does accumulate in klp-4-mutant cell bodies if receptor degradation in the multivesicular body/lysosome pathway is blocked. This study identifies kinesin KLP-4 as a novel regulator of anterograde glutamate receptor trafficking and reveals a cellular control mechanism by which receptor cargo is targeted for degradation in the absence of its motor.
巻・号 23(18)
ページ 3647-62
公開日 2012-9-1
DOI 10.1091/mbc.E12-04-0334
PII mbc.E12-04-0334
PMID 22855524
PMC PMC3442412
MeSH Amino Acid Sequence Animals Animals, Genetically Modified Caenorhabditis elegans / genetics Caenorhabditis elegans / metabolism* Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* Cyclin-Dependent Kinase 5 / genetics Cyclin-Dependent Kinase 5 / metabolism Endocytosis Green Fluorescent Proteins / genetics Green Fluorescent Proteins / metabolism Interneurons / metabolism Kinesins / genetics Kinesins / metabolism* Lysosomes / metabolism Microscopy, Fluorescence Molecular Sequence Data Multivesicular Bodies / metabolism Mutation Nerve Tissue Proteins / genetics Nerve Tissue Proteins / metabolism Nervous System / cytology Nervous System / metabolism* Protein Transport Receptors, AMPA / genetics Receptors, AMPA / metabolism* Sequence Homology, Amino Acid Signal Transduction Synapses / metabolism Time-Lapse Imaging
IF 3.791
引用数 17
WOS 分野 CELL BIOLOGY
リソース情報
線虫 tm2114