RRC ID 49554
Author Yanagihashi Y, Segawa K, Maeda R, Nabeshima YI, Nagata S.
Title Mouse macrophages show different requirements for phosphatidylserine receptor Tim4 in efferocytosis.
Journal Proc. Natl. Acad. Sci. U.S.A.
Abstract Protein S (ProS) and growth arrest-specific 6 (Gas6) bind to phosphatidylserine (PtdSer) and induce efferocytosis upon binding TAM-family receptors (Tyro3, Axl, and Mer). Here, we produced mouse ProS, Gas6, and TAM-receptor extracellular region fused to IgG fragment crystallizable region in HEK293T cells. ProS and Gas6 bound Ca2+ dependently to PtdSer (Kd 20-40 nM), Mer, and Tyro3 (Kd 15-50 nM). Gas6 bound Axl strongly (Kd < 1.0 nM), but ProS did not bind Axl. Using NIH 3T3-based cell lines expressing a single TAM receptor, we showed that TAM-mediated efferocytosis was determined by the receptor-binding ability of ProS and Gas6. Tim4 is a membrane protein that strongly binds PtdSer. Tim4 alone did not support efferocytosis, but enhanced TAM-dependent efferocytosis. Resident peritoneal macrophages, Kupffer cells, and CD169+ skin macrophages required Tim4 for TAM-stimulated efferocytosis, whereas efferocytosis by thioglycollate-elicited peritoneal macrophages or primary cultured microglia was TAM dependent, but not Tim4 dependent. These results indicate that TAM and Tim4 collaborate for efficient efferocytosis in certain macrophage populations.
Volume 114(33)
Pages 8800-8805
Published 2017-8-15
DOI 10.1073/pnas.1705365114
PII 1705365114
PMID 28768810
PMC PMC5565444
MeSH Animals Carrier Proteins / chemistry* Carrier Proteins / genetics Carrier Proteins / metabolism* HEK293 Cells Humans Intercellular Signaling Peptides and Proteins / chemistry Intercellular Signaling Peptides and Proteins / genetics Intercellular Signaling Peptides and Proteins / metabolism Macrophages, Peritoneal / metabolism* Membrane Proteins / chemistry* Membrane Proteins / genetics Membrane Proteins / metabolism* Mice Mice, Knockout NIH 3T3 Cells
IF 9.504
Resource
DNA material pCAG-HIVgp (RDB04394) CSII-EF-MCS (RDB04378) pRSV-Rev (RDB08121).