The phosphatidylserine receptor has essential functions during embryogenesis but not in apoptotic cell removal
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Your vote was cast
Thank you for your feedback
Thank you for your feedback
Gruber, Achim D
MetadataShow full item record
AbstractBackground Phagocytosis of apoptotic cells is fundamental to animal development, immune function and cellular homeostasis. The phosphatidylserine receptor (Ptdsr) on phagocytes has been implicated in the recognition and engulfment of apoptotic cells and in anti-inflammatory signaling. To determine the biological function of the phosphatidylserine receptor in vivo, we inactivated the Ptdsr gene in the mouse. Results Ablation of Ptdsr function in mice causes perinatal lethality, growth retardation and a delay in terminal differentiation of the kidney, intestine, liver and lungs during embryogenesis. Moreover, eye development can be severely disturbed, ranging from defects in retinal differentiation to complete unilateral or bilateral absence of eyes. Ptdsr -/- mice with anophthalmia develop novel lesions, with induction of ectopic retinal-pigmented epithelium in nasal cavities. A comprehensive investigation of apoptotic cell clearance in vivo and in vitro demonstrated that engulfment of apoptotic cells was normal in Ptdsr knockout mice, but Ptdsr-deficient macrophages were impaired in pro- and anti-inflammatory cytokine signaling after stimulation with apoptotic cells or with lipopolysaccharide. Conclusion Ptdsr is essential for the development and differentiation of multiple organs during embryogenesis but not for apoptotic cell removal. Ptdsr may thus have a novel, unexpected developmental function as an important differentiation-promoting gene. Moreover, Ptdsr is not required for apoptotic cell clearance by macrophages but seems to be necessary for the regulation of macrophage cytokine responses. These results clearly contradict the current view that the phosphatidylserine receptor primarily functions in apoptotic cell clearance.
CitationJournal of Biology 2004 3(4):15
PubMed Central ID549712
The following license files are associated with this item:
- A receptor for phosphatidylserine-specific clearance of apoptotic cells.
- Authors: Fadok VA, Bratton DL, Rose DM, Pearson A, Ezekewitz RA, Henson PM
- Issue date: 2000 May 4
- Clearance of apoptotic cells is not impaired in mouse embryos deficient in class A scavenger receptor types I and II (CD204).
- Authors: Komohara Y, Terasaki Y, Kaikita K, Suzuki H, Kodama T, Takeya M
- Issue date: 2005 Jan
- Phosphatidylserine receptor is required for clearance of apoptotic cells.
- Authors: Li MO, Sarkisian MR, Mehal WZ, Rakic P, Flavell RA
- Issue date: 2003 Nov 28
- Clearance of apoptotic photoreceptors: elimination of apoptotic debris into the subretinal space and macrophage-mediated phagocytosis via phosphatidylserine receptor and integrin alphavbeta3.
- Authors: Hisatomi T, Sakamoto T, Sonoda KH, Tsutsumi C, Qiao H, Enaida H, Yamanaka I, Kubota T, Ishibashi T, Kura S, Susin SA, Kroemer G
- Issue date: 2003 Jun
- Oxidized phosphatidylserine-CD36 interactions play an essential role in macrophage-dependent phagocytosis of apoptotic cells.
- Authors: Greenberg ME, Sun M, Zhang R, Febbraio M, Silverstein R, Hazen SL
- Issue date: 2006 Nov 27