Rapid cell corpse clearance by stabilin-2, a membrane phosphatidylserine receptor

Sy, Park; My, Jung; Kim, Hyung Jun; Sj, Lee; Sy, Kim; Bh, Lee; Th, Kwon; Park, RW; I-S, Kim

doi:10.1038/sj.cdd.4402242

Cited by 389 publications

(362 citation statements)

References 40 publications

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“…We previously demonstrated that stabilin-2 can specifically recognize phosphatidylserine in apoptotic cells, which enables it to mediate their engulfment [4]. Downstream signal transducing molecules, however, have not been identified in stabilin-2-mediated phagocytosis.…”

Section: Discussionmentioning

confidence: 99%

“…The ''tether'' (recognition of PS) and ''tickle'' (internalization of apoptotic cells and activation of downstream signaling pathways) mechanisms are required for the clearance of apoptotic cells [15], and it has been suggested that stabilin-2 exerts both these functions and can tether and tickle apoptotic cells alone [4]. However, in this study, thymosin b4 was not localized where the aged RBCs bind, but was localized in the area in which the phagocytic cups are formed.…”

Section: Discussionmentioning

confidence: 99%

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Thymosin β4 is involved in stabilin‐2‐mediated apoptotic cell engulfment

Lee

Park

et al. 2008

FEBS Letters

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Stabilin-2 was recently identified as a novel receptor for membrane phosphatidylserine of apoptotic cells. To identify proteins that were candidates for stabilin-2 cytoplasmic domain binding, we screened a human spleen cDNA library using the yeast two-hybrid system. We found that thymosin b4 interacts with the stabilin-2 cytoplasmic domain and is co-localized with stabilin-2 at the phagocytic cup. Knockdown of thymosin b4 significantly decreased the phagocytic activity of stabilin-2, whereas overexpression of thymosin b4 increased this activity. Additionally, amino acids 2504-2514 of stabilin-2 cytoplasmic domain were found to be responsible for the interaction with thymosin b4. Taken together, these results suggest that thymosin b4 is a downstream molecule of stabilin-2 that plays a role in stabilin-2-mediated cell corpse clearance.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Thymosin β4 is involved in stabilin‐2‐mediated apoptotic cell engulfment

Lee

Park

et al. 2008

FEBS Letters

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“…Direct recognition can occur via brainspecific angiogenesis inhibitor 1 (BAI1), 12 Stabilin-2, 13 and members of the T-cell immunoglobulin mucin domain; [14][15][16] alternatively, bridging molecules such as GAS6/Protein S and milk-fat globule EGF factor 8 can bind to the PtdSer exposed on the apoptotic cells, and in turn be recognized by members of the Tyro-Axl-Mer family and α v β 3 integrin, respectively, on the phagocyte. 17,18 Although some of these receptors only serve to tether the apoptotic cells, others can initiate intracellular signaling to induce phagocytosis.…”

Section: Steps Involved In Clearancementioning

confidence: 99%

Do not let death do us part: ‘find-me’ signals in communication between dying cells and the phagocytes

2016

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The turnover and clearance of cells is an essential process that is part of many physiological and pathological processes. Improper or deficient clearance of apoptotic cells can lead to excessive inflammation and autoimmune disease. The steps involved in cell clearance include: migration of the phagocyte toward the proximity of the dying cells, specific recognition and internalization of the dying cell, and degradation of the corpse. The ability of phagocytes to recognize and react to dying cells to perform efficient and immunologically silent engulfment has been well-characterized in vitro and in vivo. However, how apoptotic cells themselves initiate the corpse removal and also influence the cells within the neighboring environment during clearance was less understood. Recent exciting observations suggest that apoptotic cells can attract phagocytes through the regulated release of 'find-me' signals. More recent studies also suggest that these find-me signals can have additional roles outside of phagocyte attraction to help orchestrate engulfment. This review will discuss our current understanding of the different find-me signals released by apoptotic cells, how they may be relevant in vivo, and their additional roles in facilitating engulfment.

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“…BAI-1 is expressed in human monocytes and macrophages as well as in the brain and this molecule contributes both to the binding and engulfment of carboxylate-modified beads as well as apoptotic cells. Stabilin-2, a large multi-functional scavenger receptor has also been identified as a PS receptor which can mediate engulfment of apoptotic cells and aged red blood cells [17]. Other PS-dependent receptors for apoptotic cells include Mer receptor tyrosine kinase [18] and αVβ5 integrin both of which bind PS through soluble bridging molecules [19,20] while a PS independent pathway, the calreticulin/LDL-receptor-related protein (LRP)-dependent pathway has been reported for the removal of tumor targets by dendritic cells [21].…”

Section: Macrophage Scavenger Receptorsmentioning

confidence: 99%

A new role for the P2X7 receptor: a scavenger receptor for bacteria and apoptotic cells in the absence of serum and extracellular ATP

Wiley

2012

Purinergic Signalling

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The P2X7 receptor is widely recognized to mediate the proinflammatory effects of extracellular ATP. However this receptor in the absence of ATP may have a function unrelated to inflammation. Our data show that P2X7 expressed on the surface of monocyte/macrophages or on epithelial HEK-293 cells greatly augments the engulfment of latex beads and live and heat-killed bacteria by effector phagocyte in the absence of ATP and serum. The expression of P2X7 on the effector also confers the ability to phagocytose apoptotic target cells and an accumulation of P2X7 can be seen at the attachment point to the target. Activation of the P2X7 receptor by ATP causes a slow dissociation (over 10-15 min) of nonmuscle myosin from the P2X7 membrane complex and abolishes further P2X7-mediated phagocytosis of these targets. The recent crystal structure of the homologous zebrafish P2X4 receptor shows an exposed "nose" of the ectodomain (residues 115-162) which contains three of the five disulfide bonds conserved in all P2X receptors. Three short biotin-labeled peptides mimicking sequence of this exposed region bound to apoptotic target cells but not to either viable cells or to other target particles. All three peptides contained one or two cysteine residues and their replacement by alanine abolished peptide binding. These data implicate thiol-disulfide exchange reactions in the initial tethering of apoptotic cells to macrophage and establish P2X7 as one of the scavenger receptors involved in the recognition and removal of apoptotic cells in the absence of extracellular ATP and serum.

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Rapid cell corpse clearance by stabilin-2, a membrane phosphatidylserine receptor

Cited by 389 publications

References 40 publications

Thymosin β4 is involved in stabilin‐2‐mediated apoptotic cell engulfment

Thymosin β4 is involved in stabilin‐2‐mediated apoptotic cell engulfment

Do not let death do us part: ‘find-me’ signals in communication between dying cells and the phagocytes

A new role for the P2X7 receptor: a scavenger receptor for bacteria and apoptotic cells in the absence of serum and extracellular ATP

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