RRC ID 45561
Author Garafalo SD, Luth ES, Moss BJ, Monteiro MI, Malkin E, Juo P.
Title The AP2 clathrin adaptor protein complex regulates the abundance of GLR-1 glutamate receptors in the ventral nerve cord of Caenorhabditis elegans.
Journal Mol Biol Cell
Abstract Regulation of glutamate receptor (GluR) abundance at synapses by clathrin-mediated endocytosis can control synaptic strength and plasticity. We take advantage of viable, null mutations in subunits of the clathrin adaptor protein 2 (AP2) complex in Caenorhabditis elegans to characterize the in vivo role of AP2 in GluR trafficking. In contrast to our predictions for an endocytic adaptor, we found that levels of the GluR GLR-1 are decreased at synapses in the ventral nerve cord (VNC) of animals with mutations in the AP2 subunits APM-2/μ2, APA-2/α, or APS-2/σ2. Rescue experiments indicate that APM-2/μ2 functions in glr-1-expressing interneurons and the mature nervous system to promote GLR-1 levels in the VNC. Genetic analyses suggest that APM-2/μ2 acts upstream of GLR-1 endocytosis in the VNC. Consistent with this, GLR-1 accumulates in cell bodies of apm-2 mutants. However, GLR-1 does not appear to accumulate at the plasma membrane of the cell body as expected, but instead accumulates in intracellular compartments including Syntaxin-13- and RAB-14-labeled endosomes. This study reveals a novel role for the AP2 clathrin adaptor in promoting the abundance of GluRs at synapses in vivo, and implicates AP2 in the regulation of GluR trafficking at an early step in the secretory pathway.
Volume 26(10)
Pages 1887-900
Published 2015-5-15
DOI 10.1091/mbc.E14-06-1048
PII mbc.E14-06-1048
PMID 25788288
PMC PMC4436833
MeSH Adaptor Protein Complex 2 / genetics* Animals Animals, Genetically Modified Caenorhabditis elegans / genetics Caenorhabditis elegans / metabolism* Caenorhabditis elegans Proteins / genetics* Caenorhabditis elegans Proteins / metabolism Gene Expression Regulation Mutation Nervous System / metabolism* Protein Transport Receptors, AMPA / genetics Receptors, AMPA / metabolism* Synapses / genetics Synapses / metabolism*
IF 3.791
Times Cited 6
WOS Category CELL BIOLOGY
Resource
C.elegans tm2912 tm3776