Cell Corpse Engulfment Mediated by
            <i>C. elegans</i>
            Phosphatidylserine Receptor Through CED-5 and CED-12

Wang, Xiaochen; Wu, Yi-Chun; Fadok, Valerie A.; Lee, Ming Chia; Gengyo-Ando, Keiko; Cheng, Li; Ledwich, Duncan; Hsu, Pei Ken; Chen, Jia Yun; Chou, Bin Kuan; Henson, Peter M.; Mitani, Shohei; Xue, Ding

doi:10.1126/science.1087641

Cited by 187 publications

(211 citation statements)

References 25 publications

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“…Several studies using KO or knockdown animals (worm, zebrafish, and mouse) have shown that PTDSR is required for clearance of apoptotic cells (Li et al, 2003;Wang et al, 2003;Hong et al, 2004;Kunisaki et al, 2004). However, PTDSR was not essential for clearance of apoptotic cells in an analysis of another PTDSR KO mouse line .…”

Section: Ptdsrmentioning

confidence: 96%

Roles of jumonji and jumonji family genes in chromatin regulation and development

Takeuchi

Watanabe

Takano-Shimizu

et al. 2006

Developmental Dynamics

175

148

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The jumonji (jmj) gene was identified by a mouse gene trap approach and has essential roles in the development of multiple tissues. The Jmj protein has a DNA binding domain, ARID, and two conserved jmj domains (jmjN and jmjC). In many diverse species including bacteria, fungi, plants, and animals, there are many jumonji family proteins that have only the jmjC domain or both jmj domains. Recently, Jmj protein was found to be a transcriptional repressor. Several proteins in the jumonji family are involved in transcriptional repression and/or chromatin regulation. Most recently, one of the human members has been shown to be a histone demethylase, and the jmjC domain is essential for the demethylase activity. Meanwhile, more and more evidence indicating that the jumonji family proteins play important roles during development is accumulating. Many proteins in the jumonji family may regulate chromatin and gene expression, and control development through various signaling pathways. Here, we highlight the roles of jmj and jumonji family proteins in chromatin regulation and development. Developmental Dynamics 235: 2449 -2459, 2006.

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Section: Ptdsrmentioning

confidence: 96%

Roles of jumonji and jumonji family genes in chromatin regulation and development

Takeuchi

Watanabe

Takano-Shimizu

et al. 2006

Developmental Dynamics

175

148

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“…The integrin INA‐1 recognizes cell‐corpses and acts through the ced‐2/‐5/‐12 pathway in epidermal engulfing cells. Moreover, the nonreceptor tyrosine kinase SRC‐1 co‐localizes with INA‐1 in phagocytic cups and is thought to link the signal from INA‐1 to CED‐2/CrkII 66. …”

Section: Ced‐10/rac Is At the Core Of The Phagocytosis Of Apoptotic Cmentioning

confidence: 99%

“…However, since psr‐1 null mutants have a weaker engulfment defect than any of the ced‐2 , ced‐5 , or ced‐12 mutants, the contribution of this receptor to apoptotic corpse removal is thought to be minor 16, 66.…”

Section: Ced‐10/rac Is At the Core Of The Phagocytosis Of Apoptotic Cmentioning

confidence: 99%

Control of developmental networks by Rac/Rho small GTPases: How cytoskeletal changes during embryogenesis are orchestrated

et al. 2016

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Small GTPases in the Rho family act as major nodes with functions beyond cytoskeletal rearrangements shaping the Caenorhabditis elegans embryo during development. These small GTPases are key signal transducers that integrate diverse developmental signals to produce a coordinated response in the cell. In C. elegans, the best studied members of these highly conserved Rho family small GTPases, RHO‐1/RhoA, CED‐10/Rac, and CDC‐42, are crucial in several cellular processes dealing with cytoskeletal reorganization. In this review, we update the functions described for the Rho family small GTPases in spindle orientation and cell division, engulfment, and cellular movements during C. elegans embryogenesis, focusing on the Rho subfamily Rac.Please also see the video abstract here

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“…For instance, a PS receptor has been described in mammals 28 as well as in zebrafish 29 and nematodes, 30 and its expression was shown to be important for efficient cell corpse engulfment in vivo. [29][30][31][32] In contrast, recent evidence from other investigators suggests that the protein encoded by the PSR gene may not be involved in corpse clearance, but seems to be involved in the regulation of macrophage cytokine responses; 33 the discrepancies between the latter studies could be explained, at least in part, by the fact that these groups have investigated different macrophage populations, derived from mice with different genetic backgrounds. Nonetheless, our ongoing studies have provided direct evidence of PS externalization during apoptosis in Caenorhabditis elegans (unpublished findings), and PS externalization has also been documented in the slime mould Dictyostelium discoideum and in Saccharomyces cerevisiae, suggesting that this is a conserved feature of the apoptosis pathway in unicellular and multicellular organisms.…”

Section: Post Scriptummentioning

confidence: 99%

PS externalization: from corpse clearance to drug delivery

Fadeel¹,

Xue²

2005

Cell Death Differ

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Phosphatidylserine (PS) externalization on the plasma membrane of aging red blood cells and on apoptotic cell corpses serves as a common recognition signal for macrophages. 1 Perturbation of phospholipid asymmetry and rapid redistribution of PS also occurs in platelets and provides a procoagulant surface that promotes blood clotting. 2 In addition, several recent studies have revealed novel roles for altered plasma membrane phospholipid distribution in nonapoptotic cells. The aim of the present discourse is to highlight these emerging roles for PS externalization, and some of the putative therapeutic implications thereof. PS signaling is required for programmed cell clearancePhospholipid asymmetry is a common feature of all eukaryotic membranes. Moreover, mitotic and quiescent cells invest considerable amounts of energy to generate and maintain membrane lipid sidedness. Loss of phospholipid asymmetry and the concomitant externalization of PS can be readily monitored by the use of fluorescence-conjugated annexin V, an endogenous protein that specifically binds to PS, and this process has been well studied in platelets. Thus, when platelets are activated by agonists, such as thrombin and collagen, PS is rapidly brought to the surface of the cell. Exposed PS then catalyzes the assembly of proteins of the coagulation system, leading to a conversion of soluble fibrinogen into an insoluble fibrin clot. 2 The pivotal role of PS externalization is illustrated in Scott syndrome, a bleeding disorder characterized by an impaired Ca 2 þ -induced phospholipid scrambling, and hence an inability of platelets to promote blood coagulation. 2 Apoptotic cells are also procoagulant, and annexin V can completely abolish the procoagulant activity, suggesting that this effect is PS-dependent. 3 More recent findings suggest that annexin V-induced internalization of tissue factor (TF), the initiator of blood coagulation, may also contribute to the anticoagulant functions of annexin V (discussed below).The ability of PS to act as a signal for in vivo recognition and clearance of effete cells was demonstrated 20 years ago in studies of red blood cells. 4 Subsequent studies by Fadok et al. 5 showed that PS externalization also can trigger specific recognition and removal of apoptotic cells, and the exposition of PS was soon found to be a common, if not universal, event during apoptosis. 6 More recent studies have shown that PS externalization is, in fact, essential for corpse clearance by macrophages and nonprofessional phagocytes (fibroblasts). 1 Moreover, our studies have indicated that the generation of oxidized PS species (PS-OX) is an integral part of the apoptosis program. 7 Externalization of PS-OX on the cell surface potentiates macrophage engulfment of apoptotic cells, and could also serve to promote the binding of so-called bridging molecules (serum proteins) to apoptotic cell corpses. 8 Interestingly, deletion in mice of the PS-binding bridging molecule, milk fat globule epidermal growth factor 8 (MFG-E8) (also known as lactadhe...

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Cell Corpse Engulfment Mediated by C. elegans Phosphatidylserine Receptor Through CED-5 and CED-12

Cited by 187 publications

References 25 publications

Roles of jumonji and jumonji family genes in chromatin regulation and development

Roles of jumonji and jumonji family genes in chromatin regulation and development

Control of developmental networks by Rac/Rho small GTPases: How cytoskeletal changes during embryogenesis are orchestrated

PS externalization: from corpse clearance to drug delivery

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