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Merck
CN
  • CSF-1 receptor signalling is governed by pre-requisite EHD1 mediated receptor display on the macrophage cell surface.

CSF-1 receptor signalling is governed by pre-requisite EHD1 mediated receptor display on the macrophage cell surface.

Cellular signalling (2016-05-26)
Luke R Cypher, Timothy Alan Bielecki, Oluwadamilola Adepegba, Lu Huang, Wei An, Fany Iseka, Haitao Luan, Eric Tom, Matthew D Storck, Adam D Hoppe, Vimla Band, Hamid Band
摘要

Colony stimulating factor-1 receptor (CSF-1R), a receptor tyrosine kinase (RTK), is the master regulator of macrophage biology. CSF-1 can bind CSF-1R resulting in receptor activation and signalling essential for macrophage functions such as proliferation, differentiation, survival, polarization, phagocytosis, cytokine secretion, and motility. CSF-1R activation can only occur after the receptor is presented on the macrophage cell surface. This process is reliant upon the underlying macrophage receptor trafficking machinery. However, the mechanistic details governing this process are incompletely understood. C-terminal Eps15 Homology Domain-containing (EHD) proteins have recently emerged as key regulators of receptor trafficking but have not yet been studied in the context of macrophage CSF-1R signalling. In this manuscript, we utilize primary bone-marrow derived macrophages (BMDMs) to reveal a novel function of EHD1 as a regulator of CSF-1R abundance on the cell surface. We report that EHD1-knockout (EHD1-KO) macrophages cell surface and total CSF-1R levels are significantly decreased. The decline in CSF-1R levels corresponds with reduced downstream macrophage functions such as cell proliferation, migration, and spreading. In EHD1-KO macrophages, transport of newly synthesized CSF-1R to the macrophage cell surface was reduced and was associated with the shunting of the receptor to the lysosome, which resulted in receptor degradation. These findings reveal a novel and functionally important role for EHD1 in governing CSF-1R signalling via regulation of anterograde transport of CSF-1R to the macrophage cell surface.

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Sigma-Aldrich
单克隆抗 β-肌动蛋白抗体 小鼠抗, clone AC-74, ascites fluid
Sigma-Aldrich
巴弗洛霉素A1,灰色链霉菌, Bafilomycin A1, CAS 88899-55-2, acts as a highly potent and specific inhibitor of vacuolar-type H+-ATPase (Ki = 500 pM). Blocks the fusion of autophagosome with lysosome.