| 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
|
| Resource |
| Mice |
RBRC04885 |
