title: The PDZ domains of mLin-10 regulate its trans-Golgi network targeting and the surface expression of AMPA receptors.
abstract: Dynamic regulation of synaptic AMPA receptor localization underlies certain forms of synaptic plasticity and researchers are just beginning to identify molecules that may play a role in the synaptic delivery of glutamate receptors. One candidate is mLin-10, the mammalian homolog of the C. elegans receptor targeting protein LIN-10. Here, we investigated the role of mLin-10 in glutamate receptor trafficking. Cellular localization studies, in both whole brain and cultured neurons, revealed that mLin-10 is enriched in the trans-Golgi network and present in dendrites and spines--regions where protein sorting and synaptic delivery are known to occur. The specific localization of mLin-10 in Golgi is disrupted by a point mutation in an mLin-10 PDZ domain, indicating that a PDZ domain mediates this localization. Interactions between mLin-10 and glutamate receptors in both intracellular and synaptic membrane fractions were detected through biochemical assays. GST-pull down and co-immunoprecipitation experiments in heterologous cells delineated the protein domains required for interaction. These results demonstrated that glutamate receptors interact directly with mLin-10 through a PDZ domain-mediated mechanism. A PDZ point mutation enhances surface delivery of exogenous glutamate receptors in transfected neurons, suggesting that mLin-10 may regulate AMPA receptor trafficking in vivo.
authors.affiliation: Department of Neuroscience, Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, 725 N. Wolfe Street, Baltimore, MD 21205, USA.
authors.forename: Nicole L
authors.initials: NL
authors.lastname: Stricker
authors.forename: Richard L
authors.initials: RL
authors.lastname: Huganir
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D029742:Caenorhabditis elegans Proteins; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology; D006624:Hippocampus / Q000378:metabolism*; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics; D008969:Molecular Sequence Data; D011485:Protein Binding / Q000502:physiology; D020033:Protein Isoforms / Q000096:biosynthesis / Q000235:genetics; D017434:Protein Structure, Tertiary / Q000502:physiology; D011506:Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000096:biosynthesis* / Q000235:genetics; D021601:trans-Golgi Network / Q000235:genetics / Q000378:metabolism*
chemical_list: D029742:Caenorhabditis elegans Proteins; D008565:Membrane Proteins; D020033:Protein Isoforms; D011506:Proteins; D018091:Receptors, AMPA; C064105:lin-10 protein, C elegans