An Emerging Role for Voltage-Gated Na+ Channels in Cellular Migration: Regulation of Central Nervous System Development and Potentiation of Invasive Cancers

TY - JOUR

T1 - An Emerging Role for Voltage-Gated Na+ Channels in Cellular Migration: Regulation of Central Nervous System Development and Potentiation of Invasive Cancers

AU - Brackenbury, William J.

AU - Djamgoz, Mustafa B. A.

AU - Isom, Lori L.

PY - 2008/12

Y1 - 2008/12

N2 - Voltage-gated Na+ channels (VGSCs) exist as macromolecular complexes containing a pore-forming alpha subunit and one or more beta subunits. The VGSC alpha subunit gene family consists of 10 members, which have distinct tissue-specific and developmental expression profiles. So far, four beta subunits (beta 1-beta 4) and one splice variant of beta 1 (beta 1A, also called beta 1B) have been identified. VGSC beta subunits are multifunctional, serving as modulators of channel activity, regulators of channel cell surface expression, and as members of the immunoglobulin superfamily, cell adhesion molecules (CAMs) beta subunits are substrates of beta amyloid precursor protein-cleaving enzyme (BACE1) and gamma-secretase, yielding intracellular domains (ICDs) that may further modulate cellular activity via transcription. Recent evidence shows that beta 1 regulates migration and pathfinding in the developing postnatal CNS in vivo. The alpha and beta subunits, together with other components of the VGSC signaling complex, may have dynamic interactive roles depending on cell/tissue type, developmental stage, and pathophysiology. In addition to excitable cells like nerve and muscle, VGSC alpha and beta subunits are functionally expressed in cells that are traditionally considered nonexcitable, including glia, vascular endothelial cells, and cancer cells. In particular, the alpha subunits are up-regulated in line with metastatic potential and are proposed to enhance cellular migration and invasion. In contrast to the alpha subunits, beta 1 is more highly expressed in weakly metastatic cancer cells, and evidence suggests that its expression enhances cellular adhesion. Thus, novel roles are emerging for VGSC alpha and beta subunits in regulating migration during normal postnatal development of the CNS as well as during cancer metastasis. NEUROSCIENTIST 14(6):571-583, 2008. DOI: 10.1177/1073858408320293

AB - Voltage-gated Na+ channels (VGSCs) exist as macromolecular complexes containing a pore-forming alpha subunit and one or more beta subunits. The VGSC alpha subunit gene family consists of 10 members, which have distinct tissue-specific and developmental expression profiles. So far, four beta subunits (beta 1-beta 4) and one splice variant of beta 1 (beta 1A, also called beta 1B) have been identified. VGSC beta subunits are multifunctional, serving as modulators of channel activity, regulators of channel cell surface expression, and as members of the immunoglobulin superfamily, cell adhesion molecules (CAMs) beta subunits are substrates of beta amyloid precursor protein-cleaving enzyme (BACE1) and gamma-secretase, yielding intracellular domains (ICDs) that may further modulate cellular activity via transcription. Recent evidence shows that beta 1 regulates migration and pathfinding in the developing postnatal CNS in vivo. The alpha and beta subunits, together with other components of the VGSC signaling complex, may have dynamic interactive roles depending on cell/tissue type, developmental stage, and pathophysiology. In addition to excitable cells like nerve and muscle, VGSC alpha and beta subunits are functionally expressed in cells that are traditionally considered nonexcitable, including glia, vascular endothelial cells, and cancer cells. In particular, the alpha subunits are up-regulated in line with metastatic potential and are proposed to enhance cellular migration and invasion. In contrast to the alpha subunits, beta 1 is more highly expressed in weakly metastatic cancer cells, and evidence suggests that its expression enhances cellular adhesion. Thus, novel roles are emerging for VGSC alpha and beta subunits in regulating migration during normal postnatal development of the CNS as well as during cancer metastasis. NEUROSCIENTIST 14(6):571-583, 2008. DOI: 10.1177/1073858408320293

KW - Cancer

KW - Development

KW - Migration

KW - Signaling

KW - Voltage-gated Na+ channel

KW - RAT PROSTATE-CANCER

KW - BRAIN SODIUM-CHANNEL

KW - MESSENGER-RNA EXPRESSION

KW - PROTEIN-KINASE PATHWAY

KW - FEBRILE SEIZURES PLUS

KW - FUNCTIONAL EXPRESSION

KW - BETA-1 SUBUNITS

KW - ALPHA-SUBUNIT

KW - NEURITE OUTGROWTH

KW - ION CHANNELS

UR - http://www.scopus.com/inward/record.url?scp=51549097064&partnerID=8YFLogxK

U2 - 10.1177/1073858408320293

DO - 10.1177/1073858408320293

M3 - Literature review

SN - 1073-8584

VL - 14

SP - 571

EP - 583

JO - NEUROSCIENTIST

JF - NEUROSCIENTIST

IS - 6

ER -