title: Developmental and Regulatory Functions of Na(+) Channel Non-pore-forming β Subunits.
abstract: Voltage-gated Na(+) channels (VGSCs) isolated from mammalian neurons are heterotrimeric complexes containing one pore-forming α subunit and two non-pore-forming β subunits. In excitable cells, VGSCs are responsible for the initiation of action potentials. VGSC β subunits are type I topology glycoproteins, containing an extracellular amino-terminal immunoglobulin (Ig) domain with homology to many neural cell adhesion molecules (CAMs), a single transmembrane segment, and an intracellular carboxyl-terminal domain. VGSC β subunits are encoded by a gene family that is distinct from the α subunits. While α subunits are expressed in prokaryotes, β subunit orthologs did not arise until after the emergence of vertebrates. β subunits regulate the cell surface expression, subcellular localization, and gating properties of their associated α subunits. In addition, like many other Ig-CAMs, β subunits are involved in cell migration, neurite outgrowth, and axon pathfinding and may function in these roles in the absence of associated α subunits. In sum, these multifunctional proteins are critical for both channel regulation and central nervous system development.
authors: University of Michigan Neuroscience Program, Ann Arbor, MI, United States.
authors: J J
authors: JJ
authors: Winters
authors: University of Michigan Neuroscience Program, Ann Arbor, MI, United States; University of Michigan Medical School, Ann Arbor, MI, United States.
authors: L L
authors: LL
authors: Isom
mesh_terms: D000818:Animals; D001145:Arrhythmias, Cardiac / Q000378:metabolism / Q000473:pathology; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002490:Central Nervous System / Q000254:growth & development / Q000378:metabolism; D004827:Epilepsy / Q000378:metabolism / Q000473:pathology; D019143:Evolution, Molecular; D032383:Myocytes, Cardiac / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D021122:Protein Subunits / Q000737:chemistry / Q000145:classification / Q000235:genetics / Q000378:metabolism; D061566:Voltage-Gated Sodium Channels / Q000737:chemistry / Q000145:classification / Q000235:genetics / Q000378:metabolism*
chemical_list: D015815:Cell Adhesion Molecules; D021122:Protein Subunits; D061566:Voltage-Gated Sodium Channels
keywords: Axon initial segment; Axon pathfinding; Cardiac arrhythmia; Cell adhesion molecule; Cell migration; Channelome; Dravet syndrome; Epilepsy; Immunoglobulin superfamily; Neurite outgrowth; Nodes of Ranvier; Voltage-gated ion channel