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The protein-tyrosine phosphatase DEP-1 promotes migration and phagocytic activity of microglial cells in part through negative regulation of fyn tyrosine kinase.
Schneble, Nadine; Müller, Julia; Kliche, Stefanie; Bauer, Reinhard; Wetzker, Reinhard; Böhmer, Frank-D; Wang, Zhao-Qi; Müller, Jörg P.
Afiliação
  • Schneble N; Institute of Molecular Cell Biology, Center for Molecular Biomedicine (CMB), Jena University Hospital, Hans-Knöll-Straße 2, Jena, Germany.
  • Müller J; Leibniz Institute on Aging, Beutenberstraße 11, Jena, Germany.
  • Kliche S; Institute of Molecular Cell Biology, Center for Molecular Biomedicine (CMB), Jena University Hospital, Hans-Knöll-Straße 2, Jena, Germany.
  • Bauer R; Institute for Molecular and Clinical Immunology, Medical Faculty, Otto-von-Guericke-University, Leipziger Str. 44, Magdeburg, Germany.
  • Wetzker R; Institute of Molecular Cell Biology, Center for Molecular Biomedicine (CMB), Jena University Hospital, Hans-Knöll-Straße 2, Jena, Germany.
  • Böhmer FD; Institute of Molecular Cell Biology, Center for Molecular Biomedicine (CMB), Jena University Hospital, Hans-Knöll-Straße 2, Jena, Germany.
  • Wang ZQ; Institute of Molecular Cell Biology, Center for Molecular Biomedicine (CMB), Jena University Hospital, Hans-Knöll-Straße 2, Jena, Germany.
  • Müller JP; Leibniz Institute on Aging, Beutenberstraße 11, Jena, Germany.
Glia ; 65(2): 416-428, 2017 02.
Article em En | MEDLINE | ID: mdl-27859601
ABSTRACT
Microglia cells are brain macrophages whose proper functioning is essential for maintenance and repair processes of the central nervous system (CNS). Migration and phagocytosis are critical aspects of microglial activity. By using genetically modified cell lines and knockout mice we demonstrate here that the receptor protein-tyrosine phosphatase (PTP) DEP-1 (also known as PTPRJ or CD148) acts as a positive regulator of both processes in vitro and in vivo. Notably, reduced microglial migration was detectable in brains of Ptprj-/- mice using a wounding assay. Mechanistically, density-enhanced phosphatase-1 (DEP-1) may in part function by inhibiting the activity of the Src family kinase Fyn. In the microglial cell line BV2 DEP-1 depletion by shRNA-mediated knockdown resulted in enhanced phosphorylation of the Fyn activating tyrosine (Tyr420 ) and elevated specific Fyn-kinase activity in immunoprecipitates. Moreover, Fyn mRNA and protein levels were reduced in DEP-1 deficient microglia cells. Consistent with a negative regulatory role of Fyn for microglial functions, which is inhibited by DEP-1, microglial cells from Fyn-/- mice exhibited elevated migration and phagocytosis. Enhanced microglia migration to a site of injury was also observed in Fyn-/- mice in vivo. Taken together our data revealed a previously unrecognized role of DEP-1 and suggest the existence of a potential DEP-1-Fyn axis in the regulation of microglial functions. GLIA 2017;65416-428.
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Texto completo: 1 Bases de dados: MEDLINE Assunto principal: Fagocitose / Movimento Celular / Regulação da Expressão Gênica / Microglia / Proteínas Proto-Oncogênicas c-fyn Limite: Animals Idioma: En Revista: Glia Assunto da revista: NEUROLOGIA Ano de publicação: 2017 Tipo de documento: Article País de afiliação: Alemanha

Texto completo: 1 Bases de dados: MEDLINE Assunto principal: Fagocitose / Movimento Celular / Regulação da Expressão Gênica / Microglia / Proteínas Proto-Oncogênicas c-fyn Limite: Animals Idioma: En Revista: Glia Assunto da revista: NEUROLOGIA Ano de publicação: 2017 Tipo de documento: Article País de afiliação: Alemanha