K+ channel KV3.1 associates with OSP/claudin-11 and regulates oligodendrocyte development
Por:
Tiwari-Woodruff S., Beltran-Parrazal L., Charles A., Keck T., Vu T., Bronstein J.
Publicada:
1 ene 2006
Resumen:
K+ channels are differentially expressed throughout oligodendrocyte (Olg) development. KV1 family voltage-sensitive K+ channels have been implicated in proliferation and migration of Olg progenitor cell (OPC) stage, and inward rectifier K+ channels (K IR)4.1 are required for OPC differentiation to myelin-forming Olg. In this report we have identified a Shaw family K+ channel, K V3.1, that is involved in proliferation and migration of OPC and axon myelination. Application of anti-KV3.1 antibody or knockout of Kv3.1 gene decreased the sustained K+ current component of OPC by 50% and 75%, respectively. In functional assays block of KV3.1-specific currents or knockout of Kv3.1 gene inhibited proliferation and migration of OPC. Adult Kv3.1 gene-knockout mice had decreased diameter of axons and decreased thickness of myelin in optic nerves compared with age-matched wild-type littermates. Additionally, KV3.1 was identified as an associated protein of Olg-specific protein (OSP)/claudin-11 via yeast two-hybrid analysis, which was confirmed by coimmunoprecipitation and coimmunohistochemistry. In summary, the KV3.1 K+ current accounts for a significant component of the total K+ current in cells of the Olg lineage and, in association with OSP/claudin-11, plays a significant role in OPC proliferation and migration and myelination of axons. Copyright © 2006 the American Physiological Society.
Filiaciones:
Tiwari-Woodruff S.:
UCLA Multiple Sclerosis Program, Department of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, CA, United States
Glia Biology Group, UCLA Multiple Sclerosis Program, Dept. of Neurology, 635 Charles Young Dr. S., Los Angeles, CA 90095, United States
Beltran-Parrazal L.:
UCLA Multiple Sclerosis Program, Department of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, CA, United States
Charles A.:
UCLA Multiple Sclerosis Program, Department of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, CA, United States
Keck T.:
UCLA Multiple Sclerosis Program, Department of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, CA, United States
Vu T.:
UCLA Multiple Sclerosis Program, Department of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, CA, United States
Bronstein J.:
UCLA Multiple Sclerosis Program, Department of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, CA, United States
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