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The Journal of Neuroscience, May 20, 2009, 29(20):6663-6676; doi:10.1523/JNEUROSCI.5806-08.2009

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Cellular/Molecular
Golli Myelin Basic Proteins Regulate Oligodendroglial Progenitor Cell Migration through Voltage-Gated Ca²⁺ Influx

Pablo M. Paez,¹ Daniel J. Fulton,¹ Vilma Spreuer,¹ Vance Handley,¹ Celia W. Campagnoni,¹ Wendy B. Macklin,² Christopher Colwell,¹ and Anthony T. Campagnoni¹

¹Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine at UCLA, Los Angeles Medical School, Los Angeles, California 90095, and ²Department of Neurosciences, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio 44195

Correspondence should be addressed to Anthony T. Campagnoni, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine at UCLA, Neuroscience Research Building, 635 Charles Young Drive, Los Angeles, CA 90095-7332. Email: acampagnoni{at}mednet.ucla.edu

Migration of oligodendrocyte progenitor cells (OPCs) from proliferative zones to their final location in the brain is an essential step in nervous system development. Golli proteins, products of the myelin basic protein gene, can modulate voltage-gated Ca²⁺ uptake in OPCs during process extension and retraction. Given the importance of process extension/retraction on movement, the consequences of golli expression on OPC migration were examined in vivo and in vitro using time-lapse imaging of isolated OPCs and acute brain slice preparations from golli KO and golli J37 overexpressing mice (JOE). The results indicated that golli stimulated migration, and this enhanced motility was associated with increases in the activity of voltage operated Ca²⁺ channels (VOCCs). Activation of VOCCs by high K⁺ resulted in a significant increase in the migration speed of JOE OPCs versus control cells and golli-mediated modulation of OPC migration disappeared in the presence of VOCC antagonists. During migration, OPCs generated Ca²⁺ oscillations that were dependent on voltage-calcium influx and both the amplitude and frequency of these Ca²⁺ transients correlated positively with the rate of cell movement under a variety of pharmacological treatments. The Ca²⁺ transient amplitude and the rate of cell movement were significantly lower in KO cells and significantly higher in JOE cells suggesting that the presence of golli promotes OPC migration by increasing the size of voltage-mediated Ca²⁺ oscillations. These data define a new molecule that regulates Ca²⁺ homeostasis in OPCs, and are the first to demonstrate that voltage-gated Ca²⁺ channels can regulate an OPC function, such as migration.

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Received Dec. 5, 2008; revised April 9, 2009; accepted April 17, 2009.

Correspondence should be addressed to Anthony T. Campagnoni, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine at UCLA, Neuroscience Research Building, 635 Charles Young Drive, Los Angeles, CA 90095-7332. Email: acampagnoni{at}mednet.ucla.edu

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