Structure and function of the β2 subunit of brain sodium channels, a transmembrane glycoprotein with a CAM motif

Abstract

Voltage-gated sodium channels in brain neurons are complexes of a pore-forming alpha subunit with smaller beta 1 and beta 2 subunits. cDNA cloning and sequencing showed that the beta 2 subunit is a 186 residue glycoprotein with an extracellular NH2-terminal domain containing an immunoglobulin-like fold with similarity to the neural cell adhesion molecule (CAM) contactin, a single transmembrane segment, and a small intracellular domain. Coexpression of beta 2 with alpha subunits in Xenopus oocytes increases functional expression, modulates gating, and causes up to a 4-fold increase in the capacitance of the oocyte, which results from an increase in the surface area of the plasma membrane microvilli. beta 2 subunits are unique among the auxiliary subunits of ion channels in combining channel modulation with a CAM motif and the ability to expand the cell membrane surface area. They may be important regulators of sodium channel expression and localization in neurons.

Modulatory Proteins Can Rescue a Trafficking Defective Epileptogenic Nav1.1 Na+Channel Mutant

“…␤ subunits can increase Na ϩ current density and membrane insertion of wild-type ␣ subunits in some expression systems (Isom et al, 1992(Isom et al, , 1995 but not in others (Morgan et al, 2000;Qu et al, 2001;Yu et al, 2003). Thus, in some conditions, ␤ subunits can act as chaperones also for wild-type ␣ subunits, but in our experimental conditions, they did not have any significant effects.…”

A novel locus for episodic ataxia:UBR4 the likely candidate

“…The beta subunits are both predicted to form Ig folds in their extracellular domains. 31 The deletion of the extracellular domain of the beta-1 prevents sodium channel modulation. 32 Beta-1 knockout mice develop an ataxic gait and frequent generalized seizures that are followed by periods of immobility.…”

Identification of SCN3B as a novel p53-inducible proapoptotic gene

“…The b1 and b2 subunits of sodium channels have similar overall structures but are not closely related in amino-acid sequence. Both b subunits are unique among ion channel subunits in that they contain a large, glycosylated extracellular domain, a single transmembrane segment, and a small intracellular domain, and appear to have dual functions -modulation of channel gating and cell-cell interaction (Isom et al, 1992(Isom et al, , 1995. However, little is known about the function of b3 subunit.…”