TY - JOUR
T1 - SALM Synaptic Cell Adhesion-like Molecules Regulate the Differentiation of Excitatory Synapses
AU - Ko, Jaewon
AU - Kim, Seho
AU - Chung, Hye Sun
AU - Kim, Karam
AU - Han, Kihoon
AU - Kim, Hyun
AU - Jun, Heejung
AU - Kaang, Bong Kiun
AU - Kim, Eunjoon
N1 - Funding Information:
It is also possible that, rather than functioning in parallel with neuroligin, SALM2 promotes excitatory postsynaptic differentiation after trans-synaptic adhesion is established by “early” CAMs such as neuroligin. In support of this possibility, overexpression or siRNA knockdown of SALM2 had stronger effects on neurons at late stages. If this is the case, the presence of PSD-95 in the neuroligin-PSD-95 complex at early synapses may promote SALM2 recruitment through the PDZ interaction. In agreement with this, the C terminus of SALM2 was required for synaptic differentiation in the overexpression experiments. Once docked at synaptic sites, SALM2 and PSD-95 may mutually promote their synaptic recruitment and stabilization, as suggested by the SALM2 knockdown-induced dispersion of PSD-95 into small dendritic clusters and reduction in the total amount of PSD-95. In addition, PSD-95 may couple SALM2 to various PSD-95-associated postsynaptic proteins to facilitate the differentiation of early synapses. This possibility is supported by the fact that bead aggregation of SALM2 induces coclustering of PSD-95-associated GKAP.
Funding 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.
Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2006/4/20
Y1 - 2006/4/20
N2 - 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.
AB - 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.
KW - CELLBIO
KW - DEVBIO
KW - MOLNEURO
UR - http://www.scopus.com/inward/record.url?scp=33646474616&partnerID=8YFLogxK
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U2 - 10.1016/j.neuron.2006.04.005
DO - 10.1016/j.neuron.2006.04.005
M3 - Article
C2 - 16630835
AN - SCOPUS:33646474616
VL - 50
SP - 233
EP - 245
JO - Neuron
JF - Neuron
SN - 0896-6273
IS - 2
ER -