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.
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.
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Department of Physiology, School of Medicine, University of California at San Francisco, San Francisco, California 94143-0444, USA.
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D000595:Amino Acid Sequence; D000681:Amylases / Q000032:analysis* / Q000235:genetics; D000818:Animals; D001923:Brain Chemistry / Q000502:physiology*; D019556:COS Cells; D029742:Caenorhabditis elegans Proteins; D000076122:Disks Large Homolog 4 Protein; D029968:Escherichia coli Proteins; D015801:Helminth Proteins / Q000032:analysis*; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins / Q000032:analysis*; D008969:Molecular Sequence Data; D005810:Multigene Family; D009419:Nerve Tissue Proteins / Q000032:analysis* / Q000737:chemistry / Q000235:genetics; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000737:chemistry; D017386:Sequence Homology, Amino Acid; D013569:Synapses / Q000737:chemistry*
D029742:Caenorhabditis elegans Proteins; D000076122:Disks Large Homolog 4 Protein; C501449:Dlg4 protein, rat; D029968:Escherichia coli Proteins; D015801:Helminth Proteins; D047908:Intracellular Signaling Peptides and Proteins; C099173:LIN-7 protein, C elegans; C119588:LIN-7 protein, mammalian; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D016194:Receptors, N-Methyl-D-Aspartate; C033652:postsynaptic density proteins; D000681:Amylases; C108136:MalS protein, E coli