title: Oligodendroglial p130Cas is a target of Fyn kinase involved in process formation, cell migration and survival.
abstract: Oligodendrocytes are the myelinating glial cells of the central nervous system. In the course of brain development, oligodendrocyte precursor cells migrate, scan the environment and differentiate into mature oligodendrocytes with multiple cellular processes which recognize and ensheath neuronal axons. During differentiation, oligodendrocytes undergo dramatic morphological changes requiring cytoskeletal rearrangements which need to be tightly regulated. The non-receptor tyrosine kinase Fyn plays a central role in oligodendrocyte differentiation and myelination. In order to improve our understanding of the role of oligodendroglial Fyn kinase, we have identified Fyn targets in these cells. Purification and mass-spectrometric analysis of tyrosine-phosphorylated proteins in response to overexpressed active Fyn in the oligodendrocyte precursor cell line Oli-neu, yielded the adaptor molecule p130Cas. We analyzed the function of this Fyn target in oligodendroglial cells and observed that reduction of p130Cas levels by siRNA affects process outgrowth, the thickness of cellular processes and migration behavior of Oli-neu cells. Furthermore, long term p130Cas reduction results in decreased cell numbers as a result of increased apoptosis in cultured primary oligodendrocytes. Our data contribute to understanding the molecular events taking place during oligodendrocyte migration and morphological differentiation and have implications for myelin formation.
authors.affiliation: Department of Biology, Molecular Cell Biology, Johannes Gutenberg-University of Mainz, Mainz, Germany.
authors.forename: Constantin
authors.initials: C
authors.lastname: Gonsior
authors.affiliation: Department of Biology, Molecular Cell Biology, Johannes Gutenberg-University of Mainz, Mainz, Germany.
authors.forename: Fabien
authors.initials: F
authors.lastname: Binamé
authors.affiliation: Department of Biology, Molecular Cell Biology, Johannes Gutenberg-University of Mainz, Mainz, Germany.
authors.forename: Carsten
authors.initials: C
authors.lastname: Frühbeis
authors.affiliation: Institute of Physiology, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany.
authors.forename: Nina M
authors.initials: NM
authors.lastname: Bauer
authors.affiliation: Department of Biology, Molecular Cell Biology, Johannes Gutenberg-University of Mainz, Mainz, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Hoch-Kraft
authors.affiliation: Institute of Physiology, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany.
authors.forename: Heiko J
authors.initials: HJ
authors.lastname: Luhmann
authors.affiliation: Department of Biology, Molecular Cell Biology, Johannes Gutenberg-University of Mainz, Mainz, Germany.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Trotter
authors.affiliation: Institute of Physiology, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany.
authors.forename: Robin
authors.initials: R
authors.lastname: White
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism; D002465:Cell Movement / Q000502:physiology*; D002470:Cell Survival / Q000502:physiology*; D002478:Cells, Cultured; D050719:Crk-Associated Substrate Protein / Q000378:metabolism*; D051379:Mice; D009836:Oligodendroglia / Q000166:cytology / Q000378:metabolism*; D010766:Phosphorylation; D051076:Proto-Oncogene Proteins c-fyn / Q000378:metabolism*
chemical_list: D050719:Crk-Associated Substrate Protein; D051076:Proto-Oncogene Proteins c-fyn