Structure and function of the beta 2 subunit of brain sodium channels, a transmembrane glycoprotein with a CAM motif.
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.
Isom
L L
LL
Department of Pharmacology, University of Washington Seattle 98195-7280, USA.
Ragsdale
D S
DS
De Jongh
K S
KS
Westenbroek
R E
RE
Reber
B F
BF
Scheuer
T
T
Catterall
W A
WA
D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000196:embryology; D001923:Brain Chemistry / Q000502:physiology*; D015815:Cell Adhesion Molecules / Q000502:physiology*; D015816:Cell Adhesion Molecules, Neuronal; D002462:Cell Membrane / Q000502:physiology; D003001:Cloning, Molecular; D058966:Contactins; D018076:DNA, Complementary / Q000235:genetics; D015870:Gene Expression / Q000502:physiology; D007136:Immunoglobulins / Q000235:genetics; D008562:Membrane Glycoproteins / Q000502:physiology; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics; D009865:Oocytes / Q000502:physiology; D051381:Rats; D015222:Sodium Channels / Q000502:physiology* / Q000648:ultrastructure; D013116:Spinal Cord / Q000737:chemistry / Q000196:embryology; D014981:Xenopus
D015815:Cell Adhesion Molecules; D015816:Cell Adhesion Molecules, Neuronal; D058966:Contactins; D018076:DNA, Complementary; D007136:Immunoglobulins; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; D015222:Sodium Channels