Synaptic cell adhesion molecules (CAMs) are known to play key roles in various aspects of synaptic structures and functions, including early differentiation, maintenance, and plasticity. We herein report the identification of a family of cell adhesion-like molecules termed SALM that interacts with the abundant postsynaptic density (PSD) protein PSD-95. SALM2, a SALM isoform, distributes to excitatory, but not inhibitory, synaptic sites. Overexpression of SALM2 increases the number of excitatory synapses and dendritic spines. Mislocalized expression of SALM2 disrupts excitatory synapses and dendritic spines. Bead-induced direct aggregation of SALM2 results in coclustering of PSD-95 and other postsynaptic proteins, including GKAP and AMPA receptors. Knockdown of SALM2 by RNA interference reduces the number of excitatory synapses and dendritic spines and the frequency, but not amplitude, of miniature excitatory postsynaptic currents. These results suggest that SALM2 is an important regulator of the differentiation of excitatory synapses.
Bibliographical noteFunding Information:
This work was supported by the Creative Research Initiatives Program of the Korean Ministry of Science and Technology (to E.K.) and the National Research Laboratory program (to B.-K.K.). We would like to thank Moonseok Na for the help with the yeast two-hybrid screen; Drs. Daesoo Kim and Justin Lee for the help with mini analyses; Drs. Ethan Graf and Ann Marie Craig for their help with bead aggregation assays and HA-CD8 cDNA; Dr. Morgan Sheng for the NMDAR1 antibody; Dr. Yi-Ping Hsueh for the CASK antibody; the Kazusa DNA Research Institute for KIAA1246 and KIAA1484 cDNA clones; and the Core Facility Service of the 21C Frontier Brain Research Center for technical support with in situ hybridization analyses.
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