The PDZ domains of mLin-10 regulate its trans-Golgi network targeting and the surface expression of AMPA receptors.
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.
Stricker
Nicole L
NL
Department of Neuroscience, Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, 725 N. Wolfe Street, Baltimore, MD 21205, USA.
Huganir
Richard L
RL
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*
D029742:Caenorhabditis elegans Proteins; D008565:Membrane Proteins; D020033:Protein Isoforms; D011506:Proteins; D018091:Receptors, AMPA; C064105:lin-10 protein, C elegans