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J. Biol. Chem. 279 (49): 51424-51432

© 2004 by The American Society for Biochemistry and Molecular Biology, Inc.

Sodium Channel β1 Subunits Promote Neurite Outgrowth in Cerebellar Granule Neurons*

Tigwa H. Davis{ddagger}, Chunling Chen, , and Lori L. Isom§

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

Abstract: 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 β1 subunits promote neurite extension in cerebellar granule neurons. Neurons isolated from wild-type or β1(-/-) mice were plated on top of parental, mock-, or β1-transfected fibroblasts. Wild-type neurons consistently showed increased neurite length when grown on β1-transfected monolayers, whereas β1(-/-) neurons showed no increase compared with control conditions. β1-Mediated neurite extension was mimicked using a soluble β1 extracellular domain and was blocked by antibodies directed against the β1 extracellular domain. Immunohistochemical analysis suggests that the β1 and β4 subunits, but not β2 and β3, are expressed in cerebellar Bergmann glia as well as granule neurons. These results suggest a novel role for β1 during neuronal development and are the first demonstration of a functional role for sodium channel β subunit-mediated cell adhesive interactions.

Received for publication September 21, 2004.

§ 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}

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