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J. Biol. Chem., Vol. 279, Issue 49, 51424-51432, December 3, 2004

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Sodium Channel 1 Subunits Promote Neurite Outgrowth in Cerebellar Granule Neurons^*

Tigwa H. Davis, Chunling Chen, and Lori L. Isom

From the Department of Pharmacology, University of Michigan, Ann Arbor, Michigan 48109-0632

Many immunoglobulin superfamily members are integral in development through regulation of processes such as growth cone guidance, cell migration, and neurite outgrowth. We demonstrate that homophilic interactions between voltage-gated sodium channel 1 subunits promote neurite extension in cerebellar granule neurons. Neurons isolated from wild-type or 1(-/-) mice were plated on top of parental, mock-, or 1-transfected fibroblasts. Wild-type neurons consistently showed increased neurite length when grown on 1-transfected monolayers, whereas 1(-/-) neurons showed no increase compared with control conditions. 1-Mediated neurite extension was mimicked using a soluble 1 extracellular domain and was blocked by antibodies directed against the 1 extracellular domain. Immunohistochemical analysis suggests that the 1 and 4 subunits, but not 2 and 3, are expressed in cerebellar Bergmann glia as well as granule neurons. These results suggest a novel role for 1 during neuronal development and are the first demonstration of a functional role for sodium channel subunit-mediated cell adhesive interactions.

Received for publication, September 21, 2004

^* This work was supported in part by National Institutes of Health Grants R01MH59980 (to L. L. I.) and F31NS43062 (to T. H. D.). 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.

Supported by NIGMS National Institutes of Health Grant GM07767.

To whom correspondence should be addressed: Dept. of Pharmacology, The University of Michigan, 1150 W. Medical Center Dr., 1301 MSRB III, Ann Arbor, MI 48109-0632. Tel.: 734-936-3050; Fax: 734-763-4450; E-mail: lisom{at}umich.edu.

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