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Hypomyelination and increased activity of voltage-gated K+channels in mice lacking protein tyrosine phosphatase ϵ
- 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.
- Subjects :
- medicine.medical_specialty
Potassium Channels
Down-Regulation
Hyperphosphorylation
Schwann cell
Protein tyrosine phosphatase
Biology
General Biochemistry, Genetics and Molecular Biology
Kv1.5 Potassium Channel
Mice
chemistry.chemical_compound
Shab Potassium Channels
Internal medicine
Peripheral Nervous System
medicine
Animals
Molecular Biology
Cells, Cultured
Myelin Sheath
General Immunology and Microbiology
Voltage-gated ion channel
Receptor-Like Protein Tyrosine Phosphatases, Class 4
General Neuroscience
Tyrosine phosphorylation
Articles
Precipitin Tests
Mice, Mutant Strains
Cell biology
Electrophysiology
Endocrinology
medicine.anatomical_structure
nervous system
chemistry
Receptor-Like Protein Tyrosine Phosphatases
Potassium Channels, Voltage-Gated
Schwann Cells
Protein Tyrosine Phosphatases
Ion Channel Gating
Tyrosine kinase
Delayed Rectifier Potassium Channels
Protein Binding
Proto-oncogene tyrosine-protein kinase Src
Subjects
Details
- ISSN :
- 02614189
- Volume :
- 19
- Database :
- OpenAIRE
- Journal :
- The EMBO Journal
- Accession number :
- edsair.doi.dedup.....73c76630ae0d4a0079f1d951d092a22d