A Dual Role for β1

Abstract

In addition to the central pore-forming α subunit, sodium channels contain auxiliary β subunits, members of the immunoglobulin superfamily that interact with the α subunit through an extracellular immunoglobulin-like domain and thereby influence channel physiology and subcellular localization. Like other molecules in the immunoglobulin superfamily, sodium channel β subunits can act as cell adhesion molecules, leading Davis et al. to investigate the possibility that they might play a role in regulating neurite outgrowth during development. P14 to P21 mouse cerebellar granule cells plated on monolayers of 1610 Chinese hamster lung fibroblast cells (CHL cells) that were stably transfected with the sodium channel β1 subunit had longer neurites than those grown on untransfected CHL cells. Antibodies against the β1 immunoglobulin region inhibited the enhanced neurite outgrowth, whereas the β1 extracellular domain (either added directly to the medium or added through expression of a secreted truncated form of β1) promoted neurite outgrowth as effectively as full-length β1. Immunohistochemical analysis indicated that β1 was expressed in both cerebellar granule cells and Bergmann glia (which provide a substrate for granule cell migration during cerebellar development); moreover, granule cells isolated from mice that lacked β1 did not respond with enhanced neurite outgrowth when grown on CHL cells expressing β1. Thus, the sodium channel β1 subunit appears to play a role in neurite extension during development mediated through intercellular homophilic binding interactions involving its immunoglobulin-like domain. T. H. Davis, C. Chen, L. L. Isom, Sodium channel β1 subunits promote neurite outgrowth in cerebellar granule neurons. J. Biol. Chem. 279 , 51424-51432 (2004). [Abstract] [Full Text]