Glial Growth Factor/Neuregulin Inhibits Schwann Cell Myelination and Induces Demyelination
| Autor: | James L. Salzer, George Zanazzi, Mark A. Marchionni, Melanie-Jane Hannocks, Steven Einheber, Richard Westreich, Debra Bedell-Hogan |
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| Rok vydání: | 2001 |
| Předmět: |
Receptor
ErbB-3 Receptor ErbB-2 Neuregulin-1 Cellular differentiation medicine.medical_treatment Immunoblotting Schwann cell Biology neuregulin Schwann cell proliferation Phosphatidylinositol 3-Kinases erbB medicine Animals ERBB3 Phosphorylation Neuregulin 1 Cells Cultured Myelin Sheath Neurons Dose-Response Relationship Drug Growth factor Cell Differentiation Cell Biology mitogen Coculture Techniques Rats Cell biology medicine.anatomical_structure nervous system Cancer research biology.protein Neuregulin Original Article Fibroblast Growth Factor 2 demyelination Laminin Schwann Cells Schwann cell differentiation Mitogen-Activated Protein Kinases Demyelinating Diseases Signal Transduction |
| Zdroj: | The Journal of Cell Biology |
| ISSN: | 1540-8140 0021-9525 |
| Popis: | During development, neuregulin-1 promotes Schwann cell proliferation and survival; its role in later events of Schwann cell differentiation, including myelination, is poorly understood. Accordingly, we have examined the effects of neuregulin-1 on myelination in neuron-Schwann cell cocultures. Glial growth factor (GGF), a neuregulin-1 isoform, significantly inhibited myelination by preventing axonal segregation and ensheathment. Basal lamina formation was not affected. Treatment of established myelinated cultures with GGF resulted in striking demyelination that frequently began at the paranodes and progressed to the internode. Demyelination was dose dependent and accompanied by dedifferentiation of Schwann cells to a promyelinating stage, as evidenced by reexpression of the transcription factor suppressed cAMP-inducible POU; a significant proportion of cells with extensive demyelination also proliferated. Two other Schwann cell mitogens, fibroblast growth factor-2 and transforming growth factor-β, inhibited myelination but did not cause demyelination, suggesting this effect is specific to the neuregulins. The neuregulin receptor proteins, erbB2 and erbB3, are expressed on ensheathing and myelinating Schwann cells and rapidly phosphorylated with GGF treatment. GGF treatment of myelinating cultures also induced phosphorylation of phosphatidylinositol 3-kinase, mitogen-activated protein kinase, and a 120-kD protein. These results suggest that neuronal mitogens, including the neuregulins, may inhibit myelination during development and that activation of mitogen signaling pathways may contribute to the initial demyelination and subsequent Schwann cell proliferation observed in various pathologic conditions. |
| Databáze: | OpenAIRE |
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