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Hypomyelination and increased activity of voltage-gated K+channels in mice lacking protein tyrosine phosphatase ϵ

Authors :
Ari Elson
Alexander Sobko
Asher Peretz
Vera Shinder
Bernard Attali
Hava Gil-Henn
Source :
The EMBO Journal. 19:4036-4045
Publication Year :
2000
Publisher :
Wiley, 2000.

Abstract

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.

Details

ISSN :
02614189
Volume :
19
Database :
OpenAIRE
Journal :
The EMBO Journal
Accession number :
edsair.doi.dedup.....73c76630ae0d4a0079f1d951d092a22d