The PDZ domains of mLin-10 regulate its trans-Golgi network targeting and the surface expression of AMPA receptors

Neuropharmacology. 2003 Nov;45(6):837-48. doi: 10.1016/s0028-3908(03)00275-2.

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.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Caenorhabditis elegans Proteins*
  • Female
  • Gene Expression Regulation / physiology
  • Hippocampus / metabolism*
  • Membrane Proteins / biosynthesis
  • Membrane Proteins / genetics
  • Molecular Sequence Data
  • Protein Binding / physiology
  • Protein Isoforms / biosynthesis
  • Protein Isoforms / genetics
  • Protein Structure, Tertiary / physiology
  • Proteins / genetics
  • Proteins / metabolism
  • Proteins / physiology*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, AMPA / biosynthesis*
  • Receptors, AMPA / genetics
  • trans-Golgi Network / genetics
  • trans-Golgi Network / metabolism*

Substances

  • Caenorhabditis elegans Proteins
  • Membrane Proteins
  • Protein Isoforms
  • Proteins
  • Receptors, AMPA
  • lin-10 protein, C elegans