RRC ID 60836
Author Min C, Park J, Kim G, Moon H, Lee SA, Kim D, Moon B, Yang S, Lee J, Kim K, Cho H, Park J, Lee DH, Lee G, Park D.
Title Tim-4 functions as a scavenger receptor for phagocytosis of exogenous particles.
Journal Cell Death Dis
Abstract The phosphatidylserine (PS) receptor Tim-4 mediates phagocytosis of apoptotic cells by binding to PS exposed on the surface of these cells, and thus functions as a PS receptor for apoptotic cells. Some of PS receptors are capable of recognizing other molecules, such as LPS on bacteria, besides PS on apoptotic cells. However, it is unclear whether Tim-4 perceives other molecules like the PS receptors. Here, we report that Tim-4 facilitates the phagocytosis of exogenous particles as well as apoptotic cells. Similar to the process that occurs during Tim-4-mediated efferocytosis, the uptake of exogenous E. coli and S. aureus bioparticles was promoted by overexpression of Tim-4 on phagocytes, whereas phagocytosis of the bioparticles was reduced in Tim-4-deficient cells. A truncation mutant of Tim-4 lacking the cytoplasmic tail promoted phagocytosis of the particles, but a mutant lacking the IgV or the mucin domain failed to enhance phagocytosis. However, expression of Tim-4AAA (a mutant form of Tim-4 that does not bind phosphatidylserine and does not promote efferocytosis) still promoted phagocytosis. Tim-4-mediated phagocytosis was not blocked by expression of the phosphatidylserine-binding protein Anxa5. Furthermore, binding of lipopolysaccharide (LPS), which is found in the outer membrane of Gram-negative bacteria, was higher in Tim-4-overexpressing cells than in Tim-4-deficient cells. In summary, our study suggests that Tim-4 acts as a scavenger receptor and mediates phagocytosis of exogenous particles in a phosphatidylserine-independent manner.
Volume 11(7)
Pages 561
Published 2020-7-23
DOI 10.1038/s41419-020-02773-7
PII 10.1038/s41419-020-02773-7
PMID 32703939
PMC PMC7378189
MeSH Animals Apoptosis Cell Line Escherichia coli / metabolism Membrane Proteins / chemistry Membrane Proteins / metabolism* Mice, Inbred C57BL Phagocytes / metabolism Phagocytosis* Phosphatidylserines / metabolism Receptors, Scavenger / metabolism* Staphylococcus aureus / metabolism
IF 5.959
Times Cited 0
Mice RBRC04885