The role of sodium channels in cell adhesion.
Voltage-gated sodium channels are unique in that they combine action potential conduction with cell adhesion. Mammalian sodium channels are heterotrimers, composed of a central, pore-forming alpha subunit and two auxiliary beta subunits. The alpha subunits are members of a large gene family containing the voltage-gated sodium, potassium, and calcium channels. Sodium channel alpha subunits form a gene subfamily with at least eleven members. Mutations in sodium channel alpha subunit genes have been linked to paroxysmal disorders such as epilepsy, long QT syndrome (LQT), and hyperkalemic periodic paralysis in humans, and motor endplate disease and cerebellar ataxia in mice. Three genes encode the sodium channel beta subunits with at least one alternative splice product. Unlike the pore-forming alpha subunits, the sodium channel beta subunits are not structurally related to beta subunits of calcium and potassium channels. Sodium channel beta subunits are multifunctional. They modulate channel gating and regulate the level of channel expression at the plasma membrane. We have shown that beta subunits also function as cell adhesion molecules (CAMs) in terms of interaction with extracellular matrix molecules, regulation of cell migration, cellular aggregation, and interaction with the cytoskeleton. A mutation in SCN1B has been shown to cause GEFS+1 epilepsy in human families. We propose that the sodium channel signaling complex at nodes of Ranvier involves beta subunits as channel modulators as well as CAMs, other CAMs such as neurofascin and contactin, RPTPbeta, and extracellular matrix molecules such as tenascin. Finally, we explore other subunits of voltage-gated ion channels as potential CAM candidates.
Isom
Lori L
LL
Department of Pharmacology, The University of Michigan, Ann Arbor, MI 48109-0632, USA. Lisom@umich.edu
D000595:Amino Acid Sequence / Q000235:genetics; D000818:Animals; D002448:Cell Adhesion / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D006801:Humans; D008969:Molecular Sequence Data; D005810:Multigene Family; D025941:Protein Interaction Mapping; D020836:Protein Structure, Quaternary / Q000502:physiology; D015222:Sodium Channels / Q000235:genetics / Q000502:physiology*
D015222:Sodium Channels