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 ) 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;65:416-428.

Download full-text PDF

Source
http://dx.doi.org/10.1002/glia.23100DOI Listing

Publication Analysis

Top Keywords

protein-tyrosine phosphatase
8
microglial cells
8
microglia cells
8
migration phagocytosis
8
fyn microglial
8
microglial functions
8
fyn mice
8
dep-1
7
microglial
7
fyn
7

Similar Publications

Tyrosine phosphatase SHP2 accelerated ovarian cancer via modulating integrin/ E-Cadherin/ ZEB1 induced EMT.

Sci Rep

January 2025

Department of Obstetrics and Gynecology, The Fourth Hospital of Hebei Medical University, No.12, Health Road, Shijiazhuang City, 050011, Hebei Province, China.

This article focusing on examining the function and further, molecular function of SHP2 in ovarian cancer (OC). For the molecular mechanism, bioinformatics was applied to study the specifically expressed genes in ovarian cancer ; the western blotting was applied to identify the EGF, p-SHP2, ZEB1, and E-Cadherin expressions in ovarian cancer tissue and pair adjacent tissue; then SKOV3 cells were treated with EGF and infected with E-Cadherin overexpression lentivirus, and then cells were treated with benzyl butyl phthalate and IRS-1 respectively. Detection of expression of p-SHP2, ZEB1, E-Cadherin, α3-integrin, p-Src, p-SMAD2, Snail, Slug and SKOV3 cells of migration and invasion abilities were detected using Western blot method and cell scratch assay and Transwell assay; Progression of ovarian cancer was detected using subcutaneous tumor transplantation assay in nude mice and HE staining method and immunocyto.

View Article and Find Full Text PDF

Luteolin alleviates diabetic cardiac injury related to inhibiting SHP2/STAT3 pathway.

Eur J Pharmacol

January 2025

School of Basic Medical Sciences & Forensic Medicine, Hangzhou Medical College, Hangzhou 310053, China. Electronic address:

Diabetic cardiomyopathy, a heart disease resulting from diabetes mellitus, inflicts structural and functional damage to the heart. Recent studies have highlighted the potential role of luteolin, a flavonoid, in mitigating diabetic cardiovascular injuries. The Src homology 2-containing protein tyrosine phosphatase 2 (SHP2) is implicated in exacerbating diabetes- and obesity-related complications.

View Article and Find Full Text PDF

Background: Synaptic dysfunction is a central pathologic feature of Alzheimer's disease (AD), with synaptic loss even preceding neuronal loss in specific brain regions. In healthy individuals, synaptic function and plasticity are orchestrated through the complex integration of signaling inputs generated by cell surface receptors.

Methods: In this study, we investigate the role of one such receptor, protein tyrosine phosphatase receptor sigma (PTPRS), in the context of Alzheimer's disease.

View Article and Find Full Text PDF

Background: A pathological hallmark of Alzheimer's disease (AD) is the accumulation of amyloid-beta peptide (Aß). Potential treatments targeting Aß production such as γ-secretase inhibitors have had limited success. A promising alternative approach involves addressing early synaptic dysfunction by modulating molecules like striatal-enriched protein tyrosine phosphatase (STEP), whose levels and activity are upregulated by Aß.

View Article and Find Full Text PDF

New C-linked diarylheptanoid dimers as potential α-glucosidase inhibitors evidenced by biological, spectral and theoretical approaches.

Int J Biol Macromol

January 2025

Key Laboratory of Phytochemistry and Natural Medicines, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, People's Republic of China; University of Chinese Academy of Sciences, Beijing 100049, People's Republic of China. Electronic address:

Diabetes mellitus (DM) is a chronic metabolic disorder characterized by elevated blood glucose levels, generally due to defects of insulin action or secretion. Inhibition of α-glucosidase, an enzyme responsible for carbohydrate degradation, is a promising strategy for managing postprandial hyperglycemia in diabetic patients. In this study, two new C-linked diarylheptanoid dimers, kaemgalanganols A (1) and B (2), were isolated from K.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!