Characterization of MALS/Velis-1, -2, and -3: A family of mammalian LIN- 7 homologs enriched at brain synapses in association with the postsynaptic density-95/NMDA receptor postsynaptic complex

Kiwon Jo, Rachel Derin, Min Li, David S. Bredt

Research output: Contribution to journalArticlepeer-review

Abstract

Protein assembly at the postsynaptic density (PSD) of neuronal synapses is mediated in part by protein interactions with PSD-95/discs large/zona occludens-1 (PDZ) motifs. Here, we identify MALS-1, -2, -3, a family of small synaptic proteins containing little more than a single PDZ domain. MALS-1, - 2, and -3 are mammalian homologs LIN-7, a Caenorhabditis elegans protein essential for vulval development. In contrast to functions for LIN-7 in epithelial cells, MALS-1 and -2 are selectively expressed in specific neuronal populations in brain and are enriched in PSD fractions, in cultured hippocampal neurons, MALS proteins are clustered together with PSD-95 and NMDA type glutamate receptors, consistent with a postsynaptic localization for MALS proteins. Immunoprecipitation and affinity chromatography studies readily identify association of MALS with PSD-95 and an NMDA receptor subunit. The PDZ domain of MALS selectively binds to peptides terminating in E-T/S-R/X-V/I/L, which corresponds to the C terminus of NMDA type 2 receptors and numerous other ion channels at the PSD. This work suggests a role for MALS proteins in regulating recruitment of neurotransmitter receptors to the PSD.

Original languageEnglish (US)
Pages (from-to)4189-4199
Number of pages11
JournalJournal of Neuroscience
Volume19
Issue number11
DOIs
StatePublished - Jun 1 1999

Keywords

  • C. elegans
  • LIN-7
  • MALS
  • NMDA receptor
  • PDZ
  • PSD-95
  • Postsynaptic density

ASJC Scopus subject areas

  • Neuroscience(all)

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