A novel family of adhesion-like molecules that interacts with the NMDA receptor.
We have identified a novel family of synaptic adhesion-like molecules (SALMs). The family members, SALM1-SALM4, have a single transmembrane (TM) domain and contain extracellular leucine-rich repeats, an Ig C2 type domain, a fibronectin type III domain, and an intracellular postsynaptic density-95 (PSD-95)/Discs large/zona occludens-1 (PDZ) binding domain, which is present on all members except SALM4. SALM1 interacts with PSD-95, synapse-associated protein 102 (SAP102), and SAP97 based on coimmunoprecipitation of detergent-solubilized brain. Distribution studies show that SALM1 is present in synaptic membrane and postsynaptic density fractions but is also distributed in axons and dendrites. Transfection of hippocampal neurons for 4 d in vitro (DIV) with SALM1 more than doubles the dendritic lengths of neurons after 48 h, whereas transfection of neurons 14 DIV has no significant effect on neurite outgrowth. Overexpression of SALM1 in 14 DIV neurons recruits NMDA receptors (NR) and PSD-95 to dendritic puncta. This effect is dependent on the PDZ-binding domain of SALM1. SALM1 also enhances surface expression of transfected NR2A subunit. Immunoprecipitation of detergent-solubilized brain membranes with anti-SALM1 antibodies shows coimmunoprecipitation of NR1 and NR2 subunits. After transfection of heterologous cells with NR1 and NR2 cDNAs, through coimmunoprecipitation analyses, we find that SALM1 also interacts with the NMDA receptor NR1 subunit through its extracellular or TM1 domains.
Laboratory of Neurochemistry, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, Maryland 20892-8027, USA.
Chang-Yu
CY
Wang
Kai
K
Chang
Ronald S
RS
Petralia
Ya-Xian
YX
Wang
Gail K
GK
Seabold
Robert J
RJ
Wenthold
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D015816:Cell Adhesion Molecules, Neuronal / Q000737:chemistry / Q000378:metabolism*; D002478:Cells, Cultured; D000076122:Disks Large Homolog 4 Protein; D051528:Guanylate Kinases; D006624:Hippocampus / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins / Q000737:chemistry / Q000378:metabolism*; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D009474:Neurons / Q000378:metabolism*; D011485:Protein Binding; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000737:chemistry / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism*
D015816:Cell Adhesion Molecules, Neuronal; D000076122:Disks Large Homolog 4 Protein; C501447:Dlg4 protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D016194:Receptors, N-Methyl-D-Aspartate; D051528:Guanylate Kinases