Hypomyelination and increased activity of voltage-gated K(+) channels in mice lacking protein tyrosine phosphatase epsilon.
Protein tyrosine phosphatase epsilon (PTP epsilon) is strongly expressed in the nervous system; however, little is known about its physiological role. We report that mice lacking PTP epsilon exhibit hypomyelination of sciatic nerve axons at an early post-natal age. This occurs together with increased activity of delayed- rectifier, voltage-gated potassium (Kv) channels and with hyperphosphorylation of Kv1.5 and Kv2.1 Kv channel alpha-subunits in sciatic nerve tissue and in primary Schwann cells. PTP epsilon markedly reduces Kv1.5 or Kv2.1 current amplitudes in Xenopus oocytes. Kv2.1 associates with a substrate-trapping mutant of PTP epsilon, and PTP epsilon profoundly reduces Src- or Fyn-stimulated Kv2.1 currents and tyrosine phosphorylation in transfected HEK 293 cells. In all, PTP epsilon antagonizes activation of Kv channels by tyrosine kinases in vivo, and affects Schwann cell function during a critical period of Schwann cell growth and myelination.
Department of Neurobiology, The Weizmann Institute of Science, Rehovot 76100, Israel.
A
A
Peretz
H
H
Gil-Henn
A
A
Sobko
V
V
Shinder
B
B
Attali
A
A
Elson
D000818:Animals; D002478:Cells, Cultured; D051668:Delayed Rectifier Potassium Channels; D015536:Down-Regulation; D004594:Electrophysiology; D015640:Ion Channel Gating; D051666:Kv1.5 Potassium Channel; D051379:Mice; D008817:Mice, Mutant Strains; D009186:Myelin Sheath / Q000378:metabolism*; D017933:Peripheral Nervous System / Q000002:abnormalities; D015221:Potassium Channels / Q000378:metabolism*; D024642:Potassium Channels, Voltage-Gated; D011233:Precipitin Tests; D011485:Protein Binding; D017027:Protein Tyrosine Phosphatases / Q000172:deficiency*; D054630:Receptor-Like Protein Tyrosine Phosphatases, Class 4; D012583:Schwann Cells / Q000166:cytology / Q000378:metabolism*; D051669:Shab Potassium Channels
D051668:Delayed Rectifier Potassium Channels; C496982:Kcna5 protein, mouse; C496990:Kcnb1 protein, mouse; D051666:Kv1.5 Potassium Channel; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D051669:Shab Potassium Channels; D017027:Protein Tyrosine Phosphatases; C098067:Ptpre protein, mouse; D054630:Receptor-Like Protein Tyrosine Phosphatases, Class 4