Selected SALM (synaptic adhesion-like molecule) family proteins regulate synapse formation.
Synaptic cell adhesion molecules regulate various steps of synapse formation. Despite the great diversity of neuronal synapses, relatively few adhesion molecules with synaptogenic activity have been identified. Synaptic adhesion-like molecules (SALMs) are members of a family of cell adhesion molecules known to regulate neurite outgrowth and synapse maturation; however, the role of SALMs in synapse formation remains unknown. We found that expression of the SALM family proteins SALM3 and SALM5 in nonneural and neural cells induces both excitatory and inhibitory presynaptic differentiation in contacting axons. SALM3 and SALM5 proteins are enriched in synaptic fractions, and form strong (SALM3) or weak (SALM5) complexes with postsynaptic density-95 (PSD-95), an abundant postsynaptic scaffolding protein at excitatory synapses. Aggregation of SALM3, but not SALM5, on dendritic surfaces induces clustering of PSD-95. Knockdown of SALM5 reduces the number and function of excitatory and inhibitory synapses. These results suggest that selected SALM family proteins regulate synapse formation, and that SALM3 and SALM5 may promote synapse formation through distinct mechanisms.
Mah
Won
W
National Creative Research Initiative Center for Synaptogenesis, Department of Biological Sciences, KAIST, Daejeon 305-701, Korea.
Ko
Jaewon
J
Nam
Jungyong
J
Han
Kihoon
K
Chung
Woo Suk
WS
Kim
Eunjoon
E
D000818:Animals; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000502:physiology*; D002450:Cell Communication / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics; D002460:Cell Line; D002478:Cells, Cultured; D019706:Excitatory Postsynaptic Potentials / Q000235:genetics; D055785:Gene Knockdown Techniques; D006624:Hippocampus / Q000166:cytology / Q000502:physiology; D006801:Humans; D053444:Inhibitory Postsynaptic Potentials / Q000235:genetics; D008562:Membrane Glycoproteins; D051379:Mice; D005810:Multigene Family / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000502:physiology*; D019006:Neural Cell Adhesion Molecules / Q000235:genetics / Q000502:physiology*; D009433:Neural Inhibition / Q000235:genetics; D009474:Neurons / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D051381:Rats; D013569:Synapses / Q000235:genetics / Q000502:physiology*
D015815:Cell Adhesion Molecules; C000608522:Lrfn4 protein, mouse; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; D019006:Neural Cell Adhesion Molecules
Nat Rev Mol Cell Biol. 2003 Nov;4(11):833-41
14625534
J Biol Chem. 2008 Mar 28;283(13):8395-405
18227064
Prog Neurobiol. 2008 Mar;84(3):263-83
18206289
J Neurosci. 2009 Feb 4;29(5):1586-95
19193906
J Neurosci. 2004 Oct 20;24(42):9244-9
15496659
Cell. 2004 Dec 29;119(7):1013-26
15620359
J Neurosci. 1995 Jun;15(6):4328-42
7540672
Curr Opin Neurobiol. 2007 Feb;17(1):43-52
17275284
Neuron. 2009 Mar 12;61(5):650-2
19285459
Cold Spring Harb Perspect Biol. 2009 Oct;1(4):a003079
20066100
J Neurosci. 2005 Jan 26;25(4):869-79
15673667
Mol Cell Neurosci. 2009 Sep;42(1):1-10
19467332
Cell. 2000 Jun 9;101(6):657-69
10892652
Curr Opin Cell Biol. 2003 Oct;15(5):621-32
14519398
Mol Cell Neurosci. 2008 Sep;39(1):83-94
18585462
Neuron. 2005 Oct 20;48(2):171-4
16242398
Nat Rev Neurosci. 2007 Mar;8(3):206-20
17299456
Neuron. 2009 Dec 24;64(6):799-806
20064388
Nat Neurosci. 2006 Oct;9(10):1294-301
16980967
Neuron. 2009 Dec 24;64(6):791-8
20064387
Trends Neurosci. 2006 Jan;29(1):21-9
16337696
J Neurosci. 2006 Feb 22;26(8):2174-83
16495444
Neuron. 2006 Apr 20;50(2):233-45
16630835
Curr Opin Neurobiol. 2006 Feb;16(1):83-9
16427268
J Biol Chem. 2010 Apr 30;285(18):13966-78
20139422
Nature. 2008 Oct 16;455(7215):903-11
18923512
Gene. 2006 Oct 1;380(2):72-83
16828986
Nat Protoc. 2007;2(3):670-6
17406629
J Biol Chem. 2003 Feb 21;278(8):6291-300
12473661
J Neurosci Res. 2007 Oct;85(13):2824-32
17471552
Annu Rev Neurosci. 2003;26:485-508
12626697
Nat Neurosci. 2009 Apr;12(4):428-37
19252495
Neuron. 2009 Mar 12;61(5):734-49
19285470
Cell Adh Migr. 2009 Jan-Mar;3(1):29-35
19372758
J Neurosci. 2003 Mar 1;23(5):1667-77
12629171