title: Pyk2 is essential for astrocytes mobility following brain lesion.
abstract: Proline-rich tyrosine kinase 2 (Pyk2) is a calcium-dependent, non-receptor protein-tyrosine kinase of the focal adhesion kinase (FAK) family. Pyk2 is enriched in the brain, especially the forebrain. Pyk2 is highly expressed in neurons but is also present in astrocytes, where its role is not known. We used Pyk2 knockout mice (Pyk2(-/-) ) developed in our laboratory to investigate the function of Pyk2 in astrocytes. Morphology and basic properties of astrocytes in vivo and in culture were not altered in the absence of Pyk2. However, following stab lesions in the motor cortex, astrocytes-mediated wound filling was slower in Pyk2(-/-) than in wild-type littermates. In an in vitro wound healing model, Pyk2(-/-) astrocytes migrated slower than Pyk2(+/+) astrocytes. The role of Pyk2 in actin dynamics was investigated by treating astrocytic cultures with the actin-depolymerizing drug latrunculin B. Actin filaments re-polymerization after latrunculin B treatment was delayed in Pyk2(-/-) astrocytes as compared with wild-type astrocytes. We mimicked wound-induced activation by treating astrocytes in culture with tumor-necrosis factor alpha (TNFα), which increased Pyk2 phosphorylation at Tyr402. TNFα increased PKC activity, and Rac1 phosphorylation at Ser71 similarly in wild-type and Pyk2-deficient astrocytes. Conversely, we found that gelsolin, an actin-capping protein known to interact with Pyk2 in other cell types, was less enriched at the leading edge of migrating Pyk2(-/-) astrocytes, suggesting that its lack of recruitment mediated in part the effects of the mutation. This work shows the critical role of Pyk2 in astrocytes migration during wound healing.
authors.affiliation: Inserm UMR-S839, Paris, 75005, France.|Université Pierre et Marie Curie (UPMC, Paris 6), Sorbonne Universités, Paris, 75005, France.|Institut du Fer à Moulin, Paris, 75005, France.
authors.forename: Albert
authors.initials: A
authors.lastname: Giralt
authors.affiliation: Inserm UMR-S839, Paris, 75005, France.|Université Pierre et Marie Curie (UPMC, Paris 6), Sorbonne Universités, Paris, 75005, France.|Institut du Fer à Moulin, Paris, 75005, France.
authors.forename: Renata
authors.initials: R
authors.lastname: Coura
authors.affiliation: Inserm UMR-S839, Paris, 75005, France.|Université Pierre et Marie Curie (UPMC, Paris 6), Sorbonne Universités, Paris, 75005, France.|Institut du Fer à Moulin, Paris, 75005, France.
authors.forename: Jean-Antoine
authors.initials: JA
authors.lastname: Girault
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D001253:Astrocytes / Q000201:enzymology* / Q000473:pathology; D001930:Brain Injuries / Q000201:enzymology* / Q000473:pathology; D002465:Cell Movement / Q000502:physiology*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D051418:Focal Adhesion Kinase 2 / Q000235:genetics / Q000378:metabolism*; D018260:Gelsolin / Q000378:metabolism; D018345:Mice, Knockout; D009044:Motor Cortex / Q000201:enzymology* / Q000293:injuries* / Q000473:pathology; D009479:Neuropeptides / Q000378:metabolism; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014945:Wound Healing / Q000502:physiology; D020830:rac1 GTP-Binding Protein / Q000378:metabolism
chemical_list: D000199:Actins; D018260:Gelsolin; D009479:Neuropeptides; C484602:Rac1 protein, mouse; D014409:Tumor Necrosis Factor-alpha; D051418:Focal Adhesion Kinase 2; C496053:Ptk2b protein, mouse; D011493:Protein Kinase C; D020830:rac1 GTP-Binding Protein
keywords: actin polymerization; filopodia; gelsolin; lamellipodia; wound healing