scholarly journals A lysine-rich motif in the phosphatidylserine receptor PSR-1 mediates recognition and removal of apoptotic cells

2015 ◽  
Vol 6 (1) ◽  
Author(s):  
Hengwen Yang ◽  
Yu-Zen Chen ◽  
Yi Zhang ◽  
Xiaohui Wang ◽  
Xiang Zhao ◽  
...  
Keyword(s):  
Apoptotic Cells ◽  
Phosphatidylserine Receptor

Defective fetal liver erythropoiesis and T lymphopoiesis in mice lacking the phosphatidylserine receptor

Blood ◽  
2004 ◽  
Vol 103 (9) ◽  
pp. 3362-3364 ◽  
Author(s):  
Yuya Kunisaki ◽  
Sadahiko Masuko ◽  
Mayuko Noda ◽  
Ayumi Inayoshi ◽  
Terukazu Sanui ◽  
...  
Keyword(s):  
Inflammatory Responses ◽  
Apoptotic Cell ◽  
Fetal Liver ◽  
Lymphoid Cells ◽  
Cell Uptake ◽  
Developmental Defect ◽  
Apoptotic Cells ◽  
Phosphatidylserine Receptor ◽  
T Lymphopoiesis

Abstract Clearance of apoptotic cells by macrophages is considered important for prevention of inflammatory responses leading to tissue damage. The phosphatidylserine receptor (PSR), which specifically binds to phosphatidylserine (PS) exposed on the surface of apoptotic cells, mediates uptake of apoptotic cells in vitro, yet the physiologic relevance of PSR remains unknown. This issue was addressed by generating PSR-deficient (PSR-/-) mice. PSR-/- mice exhibited severe anemia and died during the perinatal period. In the PSR-/- fetal livers, erythroid differentiation was blocked at an early erythroblast stage. In addition, PSR-/- embryos exhibited thymus atrophy owing to a developmental defect of T-lymphoid cells. Clearance of apoptotic cells by macrophages was impaired in both liver and thymus of PSR-/- embryos. However, this did not induce up-regulation of inflammatory cytokines. These results indicate that during embryonic development, PSR-mediated apoptotic cell uptake is required for definitive erythropoiesis and T lymphopoiesis, independently of the prevention of inflammatory responses. (Blood. 2004;103:3362-3364)

scholarly journals The Presumptive Phosphatidylserine Receptor Is Dispensable for Innate Anti-inflammatory Recognition and Clearance of Apoptotic Cells

2005 ◽  
Vol 281 (9) ◽  
pp. 5718-5725 ◽  
Author(s):  
Justin E. Mitchell ◽  
Marija Cvetanovic ◽  
Nitu Tibrewal ◽  
Vimal Patel ◽  
Oscar R. Colamonici ◽  
...  
Keyword(s):  
Apoptotic Cells ◽  
Phosphatidylserine Receptor ◽  
Anti Inflammatory

scholarly journals The phosphatidylserine receptor TIM4 utilizes integrins as coreceptors to effect phagocytosis

2014 ◽  
Vol 25 (9) ◽  
pp. 1511-1522 ◽  
Author(s):  
Ronald S. Flannagan ◽  
Johnathan Canton ◽  
Wendy Furuya ◽  
Michael Glogauer ◽  
Sergio Grinstein
Keyword(s):  
Apoptotic Cells ◽  
Nucleotide Exchange ◽  
Wild Type ◽  
Particle Detection ◽  
Phosphatidylserine Receptor ◽  
Nucleotide Exchange Factor ◽  
Rho Family Gtpases ◽  
Rho Family ◽  
Single Particle Detection ◽  
Stimulation Of

T-cell immunoglobulin mucin protein 4 (TIM4), a phosphatidylserine (PtdSer)-binding receptor, mediates the phagocytosis of apoptotic cells. How TIM4 exerts its function is unclear, and conflicting data have emerged. To define the mode of action of TIM4, we used two distinct but complementary approaches: 1) we compared bone marrow–derived macrophages from wild-type and TIM4−/− mice, and 2) we heterologously expressed TIM4 in epithelioid AD293 cells, which rendered them competent for engulfment of PtdSer-bearing targets. Using these systems, we demonstrate that rather than serving merely as a tether, as proposed earlier by others, TIM4 is an active participant in the phagocytic process. Furthermore, we find that TIM4 operates independently of lactadherin, which had been proposed to act as a bridging molecule. Of interest, TIM4-driven phagocytosis depends on the activation of integrins and involves stimulation of Src-family kinases and focal adhesion kinase, as well as the localized accumulation of phosphatidylinositol 3,4,5-trisphosphate. These mediators promote recruitment of the nucleotide-exchange factor Vav3, which in turn activates small Rho-family GTPases. Gene silencing or ablation experiments demonstrated that RhoA, Rac1, and Rac2 act synergistically to drive the remodeling of actin that underlies phagocytosis. Single-particle detection experiments demonstrated that TIM4 and β1 integrins associate upon receptor clustering. These findings support a model in which TIM4 engages integrins as coreceptors to evoke the signal transduction needed to internalize PtdSer-bearing targets such as apoptotic cells.

scholarly journals Phosphatidylserine receptor BAI1 and apoptotic cells as new promoters of myoblast fusion

Nature ◽  
2013 ◽  
Vol 497 (7448) ◽  
pp. 263-267 ◽  
Author(s):  
Amelia E. Hochreiter-Hufford ◽  
Chang Sup Lee ◽  
Jason M. Kinchen ◽  
Jennifer D. Sokolowski ◽  
Sanja Arandjelovic ◽  
...  
Keyword(s):  
Myoblast Fusion ◽  
Apoptotic Cells ◽  
Phosphatidylserine Receptor
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