TY - JOUR
T1 - K+ channel KV3.1 associates with OSP/claudin-11 and regulates oligodendrocyte development
AU - Tiwari-Woodruff, Seema
AU - Beltran-Parrazal, Luis
AU - Charles, Andrew
AU - Keck, Thomas
AU - Vu, Trung
AU - Bronstein, Jeff
PY - 2006
Y1 - 2006
N2 - 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.
AB - 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.
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U2 - https://doi.org/10.1152/ajpcell.00510.2005
DO - https://doi.org/10.1152/ajpcell.00510.2005
M3 - Article
C2 - 16624990
SN - 0002-9513
VL - 291
SP - C687-C698
JO - AM.J.PHYSIOL.
JF - AM.J.PHYSIOL.
IS - 4
ER -