title: Deletion of the cell adhesion adaptor protein vinculin disturbs the localization of GFAP in Bergmann glial cells.
abstract: Astrocytes operate in close spatial relationship to other cells including neurons. Structural interaction is controlled by a dynamic interplay between actin-based cell motility and contact formation via cell-cell and cell-extracellular matrix adhesions. A central player in the control of cell adhesion is the cytoskeletal adaptor protein Vinculin. Incorporation of Vinculin affects mechanical properties and turnover of cell adhesion sites. To study the in vivo function of Vinculin in astrocytes, a mouse line with astrocyte specific and inducible deletion of vinculin was generated. Deletion of vinculin decreased the expression of the glial acidic fibrillary protein (GFAP) in Bergmann glial cells in the cerebellum. In addition, localization of GFAP to Bergmann glial endfeet was disturbed, indicating a role for vinculin in controlling its expression and localization. In contrast, vimentin expression, morphology, activation state and polarity of the targeted cells as well as the localization of the extracellular matrix protein laminin was not compromised. Furthermore, stab wound lesions were performed in the cerebellar cortex. In both wildtype and vinculin knockout mice GFAP expression was upregulated in Bergmann glial cells of the lesioned area with no differences observed between genotypes in expression and localization of GFAP. These results propose a selective requirement for vinculin in cellular events related to cell adhesion in vivo. As in vitro data suggested a major role for vinculin in the control of the cytoskeletal connection affecting mechanical stability and cell motility, our data add a note of caution to the extrapolation of in vitro data to in vivo function.
authors.affiliation: Carl-Ludwig-Institute for Physiology, Faculty of Medicine, University of Leipzig, Liebigstr. 27, D-04103, Leipzig, Germany.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Winkler
authors.forename: Petra G
authors.initials: PG
authors.lastname: Hirrlinger
authors.forename: Marcello
authors.initials: M
authors.lastname: Sestu
authors.forename: Franziska
authors.initials: F
authors.lastname: Wilhelm
authors.forename: Stefanie
authors.initials: S
authors.lastname: Besser
authors.forename: Alice E
authors.initials: AE
authors.lastname: Zemljic-Harpf
authors.forename: Robert S
authors.initials: RS
authors.lastname: Ross
authors.forename: Grit
authors.initials: G
authors.lastname: Bornschein
authors.forename: Ute
authors.initials: U
authors.lastname: Krügel
authors.forename: Wolfgang H
authors.initials: WH
authors.lastname: Ziegler
authors.forename: Johannes
authors.initials: J
authors.lastname: Hirrlinger
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics; D001930:Brain Injuries; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology*; D004965:Estrogen Antagonists / Q000494:pharmacology; D047629:Estrogen Receptor beta / Q000378:metabolism; D005786:Gene Expression Regulation / Q000235:genetics; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism*; D006801:Humans; D008164:Luminescent Proteins / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism*; D013629:Tamoxifen / Q000494:pharmacology; D016596:Vinculin / Q000172:deficiency*
chemical_list: D001426:Bacterial Proteins; D004965:Estrogen Antagonists; D047629:Estrogen Receptor beta; D005904:Glial Fibrillary Acidic Protein; D008164:Luminescent Proteins; C054562:yellow fluorescent protein, Bacteria; D013629:Tamoxifen; D016596:Vinculin