title: The AP2 clathrin adaptor protein complex regulates the abundance of GLR-1 glutamate receptors in the ventral nerve cord of Caenorhabditis elegans.
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.
authors: Department of Developmental, Molecular & Chemical Biology Graduate Program in Cellular and Molecular Physiology, Tufts University School of Medicine, Boston, MA 02111.
authors: Steven D
authors: SD
authors: Garafalo
authors: Department of Developmental, Molecular & Chemical Biology.
authors: Eric S
authors: ES
authors: Luth
authors: Department of Developmental, Molecular & Chemical Biology Graduate Program in Neuroscience, Sackler School of Graduate Biomedical Sciences, Tufts University School of Medicine, Boston, MA 02111.
authors: Benjamin J
authors: BJ
authors: Moss
authors: Department of Developmental, Molecular & Chemical Biology Graduate Program in Cellular and Molecular Physiology, Tufts University School of Medicine, Boston, MA 02111.
authors: Michael I
authors: MI
authors: Monteiro
authors: Department of Developmental, Molecular & Chemical Biology.
authors: Emily
authors: E
authors: Malkin
authors: Department of Developmental, Molecular & Chemical Biology peter.juo@tufts.edu.
authors: Peter
authors: P
authors: Juo
mesh_terms: D033962:Adaptor Protein Complex 2 / Q000235:genetics*; D000818:Animals; D030801:Animals, Genetically Modified; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D009154:Mutation; D009420:Nervous System / Q000378:metabolism*; D021381:Protein Transport; D018091:Receptors, AMPA / Q000235:genetics / Q000378:metabolism*; D013569:Synapses / Q000235:genetics / Q000378:metabolism*
chemical_list: D033962:Adaptor Protein Complex 2; D029742:Caenorhabditis elegans Proteins; D018091:Receptors, AMPA; C096470:glr-1 protein, C elegans