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首页> 外文期刊>Glia >The Protein-Tyrosine Phosphatase DEP-1 Promotes Migration and Phagocytic Activity of Microglial Cells in Part Through Negative Regulation of Fyn Tyrosine Kinase
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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

机译：蛋白质 - 酪氨酸磷酸酶DEM-1部分通过Fyn酪氨酸激酶的阴性调节部分促进微胶质细胞的迁移和吞噬活性

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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 (Tyr(420)) 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-1Fyn axis in the regulation of microglial functions.
机译：微胶质细胞是脑巨噬细胞，其适当的功能对于中枢神经系统（CNS）的维护和修复过程至关重要。迁移和吞噬作用是小胶质过程的关键方面。通过使用基因改性的细胞系和敲除小鼠，我们在此证明受体蛋白 - 酪氨酸磷酸酶（PTP）DEP-1（也称为PTPRJ或CD148）用作体外和体内两种方法的正调节剂。值得注意的是，使用伤口测定法在PTPRJ（ - / - ）小鼠的大脑中可检测到降低的微胶质迁移。机械上，密度增强的磷酸酶-1（DEP-1）可以通过抑制SRC家族激酶FYN的活性部分功能。在微胶质细胞系BV2 DEP-1通过SHRNA介导的敲低耗尽导致Fyn活化酪氨酸（TYR（420））的增强磷酸化，并在免疫沉淀物中升高了特异性Fyn-kinase活性。此外，在DEP-1缺陷型微胶质细胞中降低了FYN mRNA和蛋白质水平。对于Syp-1抑制的微胶质功能的FIN的阴性调节作用一致，来自FYN（ - / - ）小鼠的小胶质细胞表现出升高的迁移和吞噬作用。在体内的Fyn（/ - / - ）小鼠中也观察到增强的小胶质细胞迁移到损伤部位。我们的数据携带，揭示了DEP-1的先前未被识别的作用，并提出了在微胶囊功能的调节中存在潜在的DEP-1FYN轴的存在。

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