PMID- 27224507 OWN - NLM STAT- MEDLINE DCOM- 20171128 LR - 20221029 IS - 1873-3913 (Electronic) IS - 0898-6568 (Print) IS - 0898-6568 (Linking) VI - 28 IP - 9 DP - 2016 Sep TI - CSF-1 receptor signalling is governed by pre-requisite EHD1 mediated receptor display on the macrophage cell surface. PG - 1325-1335 LID - S0898-6568(16)30114-0 [pii] LID - 10.1016/j.cellsig.2016.05.013 [doi] AB - 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. CI - Copyright (c) 2016 Elsevier Inc. All rights reserved. FAU - Cypher, Luke R AU - Cypher LR AD - Eppley Cancer Institute for Research in Cancer & Allied Diseases, University of Nebraska Medical Center, Omaha, NE, United States. FAU - Bielecki, Timothy Alan AU - Bielecki TA AD - Eppley Cancer Institute for Research in Cancer & Allied Diseases, University of Nebraska Medical Center, Omaha, NE, United States. FAU - Huang, Lu AU - Huang L AD - Department of Chemistry and Biochemistry, BioSNTR, South Dakota State University, Brookings, SD, United States. FAU - An, Wei AU - An W AD - Department of Genetics, Cell Biology, & Anatomy, University of Nebraska Medical Center, Omaha, NE, United States. FAU - Iseka, Fany AU - Iseka F AD - Department of Genetics, Cell Biology, & Anatomy, University of Nebraska Medical Center, Omaha, NE, United States. FAU - Tom, Eric AU - Tom E AD - Department of Biochemistry & Molecular Biology, University of Nebraska Medical Center, Omaha, NE, United States. FAU - Storck, Matthew D AU - Storck MD AD - Eppley Cancer Institute for Research in Cancer & Allied Diseases, University of Nebraska Medical Center, Omaha, NE, United States. FAU - Hoppe, Adam D AU - Hoppe AD AD - Department of Chemistry and Biochemistry, BioSNTR, South Dakota State University, Brookings, SD, United States. FAU - Band, Vimla AU - Band V AD - Eppley Cancer Institute for Research in Cancer & Allied Diseases, University of Nebraska Medical Center, Omaha, NE, United States; Department of Genetics, Cell Biology, & Anatomy, University of Nebraska Medical Center, Omaha, NE, United States. FAU - Band, Hamid AU - Band H AD - Eppley Cancer Institute for Research in Cancer & Allied Diseases, University of Nebraska Medical Center, Omaha, NE, United States; Department of Genetics, Cell Biology, & Anatomy, University of Nebraska Medical Center, Omaha, NE, United States. Electronic address: hband@unmc.edu. LA - eng GR - R01 CA087986/CA/NCI NIH HHS/United States GR - R01 CA096844/CA/NCI NIH HHS/United States GR - R01 CA116552/CA/NCI NIH HHS/United States GR - P30 GM106397/GM/NIGMS NIH HHS/United States GR - R01 CA144027/CA/NCI NIH HHS/United States GR - R01 CA105489/CA/NCI NIH HHS/United States GR - P30 CA036727/CA/NCI NIH HHS/United States GR - R01 CA099163/CA/NCI NIH HHS/United States GR - T32 CA009476/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, U.S. Gov't, Non-P.H.S. DEP - 20160517 PL - England TA - Cell Signal JT - Cellular signalling JID - 8904683 RN - 0 (Autoantigens) RN - 0 (Ehd1 protein, mouse) RN - 0 (Golgin subfamily A member 2) RN - 0 (Macrolides) RN - 0 (Membrane Proteins) RN - 0 (Vesicular Transport Proteins) RN - 81627-83-0 (Macrophage Colony-Stimulating Factor) RN - 88899-55-2 (bafilomycin A1) RN - EC 2.7.10.1 (Receptor, Macrophage Colony-Stimulating Factor) SB - IM EIN - Cell Signal. 2016 Dec;28(12):1933. PMID: 27510742 MH - Animals MH - Autoantigens/metabolism MH - Cell Compartmentation/drug effects MH - Cell Membrane/drug effects/*metabolism MH - Cell Movement/drug effects MH - Cell Proliferation/drug effects MH - Lysosomes/drug effects/metabolism MH - Macrolides/pharmacology MH - Macrophage Colony-Stimulating Factor/metabolism MH - Macrophages/*cytology/drug effects/*metabolism MH - Membrane Proteins/metabolism MH - Mice, Inbred C57BL MH - Mice, Knockout MH - Protein Biosynthesis/drug effects MH - Proteolysis/drug effects MH - Receptor, Macrophage Colony-Stimulating Factor/*metabolism MH - *Signal Transduction/drug effects MH - Vesicular Transport Proteins/*metabolism PMC - PMC5045265 MID - NIHMS796235 OTO - NOTNLM OT - CSF-1R OT - Cell signalling OT - Cell surface OT - Macrophage OT - Proliferation OT - Receptor tyrosine kinase EDAT- 2016/05/26 06:00 MHDA- 2017/11/29 06:00 PMCR- 2017/09/01 CRDT- 2016/05/26 06:00 PHST- 2016/04/22 00:00 [received] PHST- 2016/05/13 00:00 [revised] PHST- 2016/05/16 00:00 [accepted] PHST- 2016/05/26 06:00 [entrez] PHST- 2016/05/26 06:00 [pubmed] PHST- 2017/11/29 06:00 [medline] PHST- 2017/09/01 00:00 [pmc-release] AID - S0898-6568(16)30114-0 [pii] AID - 10.1016/j.cellsig.2016.05.013 [doi] PST - ppublish SO - Cell Signal. 2016 Sep;28(9):1325-1335. doi: 10.1016/j.cellsig.2016.05.013. Epub 2016 May 17.