K+ channel KV3.1 associates with OSP/claudin-11 and regulates oligodendrocyte development.
K(+) channels are differentially expressed throughout oligodendrocyte (Olg) development. K(V)1 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(V)3.1, that is involved in proliferation and migration of OPC and axon myelination. Application of anti-K(V)3.1 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 K(V)3.1-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, K(V)3.1 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 K(V)3.1 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.
Tiwari-Woodruff
Seema
S
UCLA Multiple Sclerosis Program, Department of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, California 90095, USA. seemaw@ucla.edu
Beltran-Parrazal
Luis
L
Charles
Andrew
A
Keck
Thomas
T
Vu
Trung
T
Bronstein
Jeff
J
D000818:Animals; D001369:Axons / Q000502:physiology / Q000648:ultrastructure; D002455:Cell Division / Q000502:physiology; D019070:Cell Lineage; D002465:Cell Movement / Q000502:physiology; D057167:Claudins; D004553:Electric Conductivity; D004594:Electrophysiology; D007150:Immunohistochemistry; D051379:Mice; D018345:Mice, Knockout; D009186:Myelin Sheath / Q000502:physiology / Q000648:ultrastructure; D009419:Nerve Tissue Proteins / Q000502:physiology*; D009836:Oligodendroglia / Q000166:cytology / Q000502:physiology*; D009900:Optic Nerve / Q000648:ultrastructure; D012333:RNA, Messenger / Q000378:metabolism; D051670:Shaw Potassium Channels / Q000172:deficiency / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D013234:Stem Cells / Q000378:metabolism
D057167:Claudins; C492354:Cldn11 protein, mouse; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D051670:Shaw Potassium Channels