Mouse macrophages show different requirements for phosphatidylserine receptor Tim4 in efferocytosis.

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 (K_d 20-40 nM), Mer, and Tyro3 (K_d 15-50 nM). Gas6 bound Axl strongly (K_d < 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, b

SUBMITTER: Yanagihashi Y 

PROVIDER: S-EPMC5565444 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature