title: Mutations in the ligand-binding and pore domains control exit of glutamate receptors from the endoplasmic reticulum in C. elegans.
abstract: The abundance of ion channels and neurotransmitter receptors in the plasma membrane is limited by the efficiency of protein folding and subunit assembly in the endoplasmic reticulum (ER). The ER has a quality-control system for monitoring nascent proteins, which prevents incompletely folded and assembled proteins from being transported from the ER. Chaperone proteins identify unfolded and misassembled proteins in the ER via retention motifs that are normally buried at intersubunit contacts or via carbohydrate residues that are attached to misfolded domains. Here, we examined the trafficking of a C. elegans non-NMDA glutamate receptor (GLR-1). We show that mutations in the pore domain (predicted to block ion permeation) and mutations in the ligand-binding domain (predicted to block glutamate binding) both caused a dramatic reduction in the synaptic abundance of GLR-1 and increased retention of GLR-1 in the ER. These results suggest that the structural integrity of the ligand-binding site and the pore domain of GLR-1 are monitored in the ER during the process of quality control.
authors.affiliation: Department of Molecular Biology, Massachusetts General Hospital, Harvard Medical School, 50 Blossom St., Wellman 8, Boston, MA 02114, USA.
authors.forename: Maria E
authors.initials: ME
authors.lastname: Grunwald
authors.forename: Joshua M
authors.initials: JM
authors.lastname: Kaplan
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins / Q000235:genetics* / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000235:genetics / Q000378:metabolism*; D008024:Ligands; D009154:Mutation; D011485:Protein Binding / Q000235:genetics; D021381:Protein Transport / Q000235:genetics; D018091:Receptors, AMPA / Q000235:genetics* / Q000378:metabolism*; D017470:Receptors, Glutamate / Q000235:genetics / Q000378:metabolism*
chemical_list: D029742:Caenorhabditis elegans Proteins; D008024:Ligands; D018091:Receptors, AMPA; D017470:Receptors, Glutamate