|
Sign In to gain access to subscriptions and/or personal tools.
|
An Emerging Role for Voltage-Gated Na+ Channels in Cellular Migration: Regulation of Central Nervous System Development and Potentiation of Invasive Cancers
William J. Brackenbury1,
Mustafa B. A. Djamgoz2,
and
Lori L. Isom1*
1 Department of Pharmacology, University of Michigan Medical School, Ann Arbor, Michigan
2 Neuroscience Solutions to Cancer Research Group, Division of Cell and Molecular Biology, Imperial College London, United Kingdom
* To whom correspondence should be addressed. E-mail: lisom{at}umich.edu.
 |
Abstract |
|---|
Voltage-gated Na+ channels (VGSCs) exist as macromolecular complexes containing a pore-forming  subunit and one or more  subunits. The VGSC subunit gene family consists of 10 members, which have distinct tissue-specific and developmental expression profiles. So far, four subunits (1–4) and one splice variant of 1 (1A, also called 1B) have been identified. VGSC 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). subunits are substrates of -amyloid precursor protein-cleaving enzyme (BACE1) and  -secretase, yielding intracellular domains (ICDs) that may further modulate cellular activity via transcription. Recent evidence shows that 1 regulates migration and pathfinding in the developing postnatal CNS in vivo. The and 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 and subunits are functionally expressed in cells that are traditionally considered nonexcitable, including glia, vascular endothelial cells, and cancer cells. In particular, the subunits are up-regulated in line with metastatic potential and are proposed to enhance cellular migration and invasion. In contrast to the subunits, 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 and subunits in regulating migration during normal postnatal development of the CNS as well as during cancer metastasis. NEUROSCIENTIST XX(X):xx–xx, XXXX. DOI: 10.1177/1073858408320293
First published on October 20, 2008, doi:10.1177/1073858408320293
The Neuroscientist 2008;14:571.
A more recent version of this article appeared on December 1, 2008
 CiteULike  Complore  Connotea  Del.icio.us  Digg  Reddit  Technorati  Twitter What's this?
This article has been cited by other articles:
|
|
|
|
 
G. A. Patino, L. R. F. Claes, L. F. Lopez-Santiago, E. A. Slat, R. S. R. Dondeti, C. Chen, H. A. O'Malley, C. B. B. Gray, H. Miyazaki, N. Nukina, et al.
A Functional Null Mutation of SCN1B in a Patient with Dravet Syndrome
J. Neurosci.,
August 26, 2009;
29(34):
10764 - 10778.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W.-C. Sin, D. M. Moniz, M. A. Ozog, J. E. Tyler, M. Numata, and J. Church
Regulation of Early Neurite Morphogenesis by the Na+/H+ Exchanger NHE1
J. Neurosci.,
July 15, 2009;
29(28):
8946 - 8959.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Krupinski and G. J. Beitel
Unexpected Roles of the Na-K-ATPase and Other Ion Transporters in Cell Junctions and Tubulogenesis
Physiology,
June 1, 2009;
24(3):
192 - 201.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. J. Fein, M. A. Wright, E. A. Slat, A. B. Ribera, and L. L. Isom
scn1bb, a Zebrafish Ortholog of SCN1B Expressed in Excitable and Nonexcitable Cells, Affects Motor Neuron Axon Morphology and Touch Sensitivity
J. Neurosci.,
November 19, 2008;
28(47):
12510 - 12522.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
