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J. Biol. Chem., Vol. 283, Issue 13, 8395-8405, March 28, 2008

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The SALM Family of Adhesion-like Molecules Forms Heteromeric and Homomeric Complexes^*

From the Laboratory of Neurochemistry, NIDCD, National Institutes of Health, Bethesda, Maryland 20892-8027

Synaptic adhesion-like molecules (SALMs) are a newly discovered family of adhesion molecules that play roles in synapse formation and neurite outgrowth. The SALM family is comprised of five homologous molecules that are expressed largely in the central nervous system. SALMs 1–3 contain PDZ-binding domains, whereas SALMs 4 and 5 do not. We are interested in characterizing the interactions of the SALMs both among the individual members and with other binding partners. In the present study, we focused on the interactions formed by the five SALM members in rat brain and heterologous cells. In brain, we found that SALMs 1–3 strongly co-immunoprecipitated with each other, whereas SALMs 4 and 5 did not, suggesting that SALMs 4 and 5 mainly form homomeric complexes. In heterologous cells transfected with SALMs, co-immunoprecipitation studies showed that all five SALMs form heteromeric and homomeric complexes. We also determined if SALMs could form trans-cellular associations between transfected heterologous cells. Both SALMs 4 and 5 formed homophilic, but not heterophilic associations, whereas no trans associations were formed by the other SALMs. The ability of SALM4 to form trans interactions is due to its extracellular N terminus because chimeras of SALM4 N terminus and SALM2 C terminus can form trans interactions, whereas chimeras of SALM2 N terminus and SALM4 C terminus cannot. Co-culture experiments using HeLa cells and rat hippocampal neurons expressing the SALMs showed that SALM4 is recruited to points of contact between the cells. In neurons, these points of contact were seen in both axons and dendrites.

Received for publication, November 19, 2007 , and in revised form, January 10, 2008.

^* This work was supported by the National Institutes of Health NIDCD Intramural Research Program. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The on-line version of this article (available at http://www.jbc.org) contains supplemental Figs. S1 and methods.

¹ To whom correspondence should be addressed: 50 South Dr., Bldg. 50, Rm. 4140, Bethesda, MD 20892-8027. Tel.: 301-496-6530; Fax: 301-480-2324; E-mail: wenthold{at}nidcd.nih.gov.

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