CDK-5 regulates the abundance of GLR-1 glutamate receptors in the ventral cord of Caenorhabditis elegans.
The proline-directed kinase Cdk5 plays a role in several aspects of neuronal development. Here, we show that CDK-5 activity regulates the abundance of the glutamate receptor GLR-1 in the ventral cord of Caenorhabditis elegans and that it produces corresponding changes in GLR-1-dependent behaviors. Loss of CDK-5 activity results in decreased abundance of GLR-1 in the ventral cord, accompanied by accumulation of GLR-1 in neuronal cell bodies. Genetic analysis of cdk-5 and the clathrin adaptin unc-11 AP180 suggests that CDK-5 functions prior to endocytosis at the synapse. The scaffolding protein LIN-10/Mint-1 also regulates GLR-1 abundance in the nerve cord. CDK-5 phosphorylates LIN-10/Mint-1 in vitro and bidirectionally regulates the abundance of LIN-10/Mint-1 in the ventral cord. We propose that CDK-5 promotes the anterograde trafficking of GLR-1 and that phosphorylation of LIN-10 may play a role in this process.
Juo
Peter
P
Department of Molecular Biology, Massachusetts General Hospital, and Department of Genetics, Harvard Medical School, Boston, MA 02114, USA. peter.juo@tufts.edu
Harbaugh
Tom
T
Garriga
Gian
G
Kaplan
Joshua M
JM
D000818:Animals; D017173:Caenorhabditis elegans / Q000201:enzymology*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism*; D051360:Cyclin-Dependent Kinase 5 / Q000737:chemistry / Q000378:metabolism*; D015536:Down-Regulation / Q000235:genetics; D004705:Endocytosis; D008565:Membrane Proteins / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D009420:Nervous System / Q000201:enzymology*; D010766:Phosphorylation; D017434:Protein Structure, Tertiary; D021122:Protein Subunits / Q000378:metabolism; D050683:R-SNARE Proteins / Q000378:metabolism; D018091:Receptors, AMPA / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism
D029742:Caenorhabditis elegans Proteins; D008565:Membrane Proteins; D021122:Protein Subunits; D050683:R-SNARE Proteins; D018091:Receptors, AMPA; D011993:Recombinant Fusion Proteins; C096470:glr-1 protein, C elegans; C064105:lin-10 protein, C elegans; D051360:Cyclin-Dependent Kinase 5