The kinesin-3 family motor KLP-4 regulates anterograde trafficking of GLR-1 glutamate receptors in the ventral nerve cord ofCaenorhabditis elegans

Autor: Shikha Ahlawat, Peter Juo, Jennifer R. Kowalski, Sandhya P. Koushika, Michael I. Monteiro, Emily Malkin
Rok vydání: 2012
Předmět:
Nervous system
Green Fluorescent Proteins
Molecular Sequence Data
Kinesins
Nerve Tissue Proteins
Nervous System
Time-Lapse Imaging
Clathrin
Animals
Genetically Modified
03 medical and health sciences
0302 clinical medicine
Interneurons
medicine
Animals
Amino Acid Sequence
Receptors
AMPA
Caenorhabditis elegans
Caenorhabditis elegans Proteins
Receptor
Molecular Biology
030304 developmental biology
0303 health sciences
Sequence Homology
Amino Acid
biology
fungi
Multivesicular Bodies
Glutamate receptor
Cyclin-Dependent Kinase 5
Articles
Cell Biology
biology.organism_classification
Endocytosis
Cell biology
Protein Transport
medicine.anatomical_structure
Microscopy
Fluorescence
Membrane Trafficking
Ventral nerve cord
Mutation
Synapses
biology.protein
Kinesin
Ap180
Lysosomes
030217 neurology & neurosurgery
Signal Transduction
Zdroj: Molecular Biology of the Cell
ISSN: 1939-4586
1059-1524
DOI: 10.1091/mbc.e12-04-0334
Popis: Cyclin-dependent kinase-5 and the kinesin-3 family motor KLP-4 function in the same pathway to promote anterograde trafficking of glutamate receptors in the ventral nerve cord of Caenorhabditis elegans. This study reveals a cellular control mechanism by which receptor cargo is targeted for degradation in the absence of its motor.
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.
Databáze: OpenAIRE
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