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Interaction between the integrin Mac-1 and signal regulatory protein (SIRP) mediates fusion in heterologous cells
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SYSNO ASEP 0507816 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Interaction between the integrin Mac-1 and signal regulatory protein (SIRP) mediates fusion in heterologous cells Author(s) Podolnikova, N. P. (US)
Hlaváčková, Markéta (FGU-C) RID, ORCID
Wu, Y. (US)
Yakubenko, V. P. (US)
Faust, J. (US)
Balabiyev, A. (US)
Wang, X. (US)
Ugarova, T. P. (US)Source Title Journal of Biological Chemistry. - : Elsevier - ISSN 0021-9258
Roč. 294, č. 19 (2019), s. 7833-7849Number of pages 17 s. Language eng - English Country US - United States Keywords integrin ; cell adhesion ; cell-cell interaction ; structure-function ; macrophage ; cell-cell fusion ; chronic inflammation Subject RIV ED - Physiology OECD category Physiology (including cytology) Method of publishing Open access with time embargo (10.05.2020) Institutional support FGU-C - RVO:67985823 UT WOS 000470153300025 EID SCOPUS 85066002918 DOI 10.1074/jbc.RA118.006314 Annotation Macrophage fusion leading to the formation of multinucleated giant cells is a hallmark of chronic inflammation. Several membrane proteins have been implicated in mediating cell-cell attachment during fusion, but their binding partners remain unknown. Recently, we demonstrated that interleukin-4 (IL-4)-induced fusion of mouse macrophages depends on the integrin macrophage antigen 1 (Mac-1). Surprisingly, the genetic deficiency of intercellular adhesion molecule 1 (ICAM-1), an established ligand of Mac-1, did not impair macrophage fusion, suggesting the involvement of other counter-receptors. Here, using various approaches, including signal regulatory protein (SIRP) knockdown, recombinant proteins, adhesion and fusion assays, biolayer interferometry, and peptide libraries, we show that SIRP, which, similar to ICAM-1, belongs to the Ig superfamily and has previously been implicated in cell fusion, interacts with Mac-1. The following results support the conclusion that SIRP is a ligand of Mac-1: (a) recombinant ectodomain of SIRP supports adhesion of Mac-1-expressing cells, (b) Mac-1-SIRP interaction is mediated through the ligand-binding I-M-domain of Mac-1, (c) recognition of SIRP by the I-M-domain conforms to general principles governing binding of Mac-1 to many of its ligands, (d) SIRP reportedly binds CD47, however, anti-CD47 function-blocking mAb produced only a limited inhibition of macrophage adhesion to SIRP, and (e) co-culturing of SIRP- and Mac-1-expressing HEK293 cells resulted in the formation of multinucleated cells. Taken together, these results identify SIRP as a counter-receptor for Mac-1 and suggest that the Mac-1-SIRP interaction may be involved in macrophage fusion. Workplace Institute of Physiology Contact Lucie Trajhanová, lucie.trajhanova@fgu.cas.cz, Tel.: 241 062 400 Year of Publishing 2020 Electronic address https://www.jbc.org/content/294/19/7833
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