title: The kinesin-3 family motor KLP-4 regulates anterograde trafficking of GLR-1 glutamate receptors in the ventral nerve cord of Caenorhabditis elegans.
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.
authors.affiliation: Department of Molecular Physiology and Pharmacology, Tufts University School of Medicine, Boston, MA 02111, USA.
authors.forename: Michael I
authors.initials: MI
authors.lastname: Monteiro
authors.forename: Shikha
authors.initials: S
authors.lastname: Ahlawat
authors.forename: Jennifer R
authors.initials: JR
authors.lastname: Kowalski
authors.forename: Emily
authors.initials: E
authors.lastname: Malkin
authors.forename: Sandhya P
authors.initials: SP
authors.lastname: Koushika
authors.forename: Peter
authors.initials: P
authors.lastname: Juo
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D030801:Animals, Genetically Modified; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D051360:Cyclin-Dependent Kinase 5 / Q000235:genetics / Q000378:metabolism; D004705:Endocytosis; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D007395:Interneurons / Q000378:metabolism; D016547:Kinesins / Q000235:genetics / Q000378:metabolism*; D008247:Lysosomes / Q000378:metabolism; D008856:Microscopy, Fluorescence; D008969:Molecular Sequence Data; D057146:Multivesicular Bodies / Q000378:metabolism; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009420:Nervous System / Q000166:cytology / Q000378:metabolism*; D021381:Protein Transport; D018091:Receptors, AMPA / Q000235:genetics / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D013569:Synapses / Q000378:metabolism; D059008:Time-Lapse Imaging
chemical_list: D029742:Caenorhabditis elegans Proteins; D009419:Nerve Tissue Proteins; D018091:Receptors, AMPA; C096470:glr-1 protein, C elegans; C120753:unc-11 protein, C elegans; D049452:Green Fluorescent Proteins; D051360:Cyclin-Dependent Kinase 5; C578567:KLP-4 protein, C elegans; D016547:Kinesins