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Phagocytes express multiple phosphatidylserine (PtdSer) receptors that recognize apoptotic cells. It is unknown whether these receptors are interchangeable or if they play unique roles during cell clearance. Loss of the PtdSer receptor Mertk is associated with apoptotic corpse accumulation in the testes and degeneration of photoreceptors in the eye. Both phenotypes are linked to impaired phagocytosis by specialized phagocytes: Sertoli cells and the retinal pigmented epithelium (RPE). Here, we overexpressed the PtdSer receptor BAI1 in mice lacking MerTK (Mertk(-/-) Bai1(Tg)) to evaluate PtdSer receptor compensation in vivo. While Bai1 overexpression rescues clearance of apoptotic germ cells in the testes of Mertk(-/-) mice it fails to enhance RPE phagocytosis or prevent photoreceptor degeneration. To determine why MerTK is critical to RPE function, we examined visual cycle intermediates and performed unbiased RNAseq analysis of RPE from Mertk(+/+) and Mertk(-/-) mice. Prior to the onset of photoreceptor degeneration, Mertk(-/-) mice had less accumulation of retinyl esters and dysregulation of a striking array of genes, including genes related to phagocytosis, metabolism, and retinal disease in humans. Collectively, these experiments establish that not all phagocytic receptors are functionally equal, and that compensation among specific engulfment receptors is context and tissue dependent.
Keywords
PIGMENT EPITHELIAL-CELLS, CARBONIC-ANHYDRASE-IV, APOPTOTIC CELLS, RETINITIS-PIGMENTOSA, PATHOLOGICAL MYOPIA, TYROSINE KINASE, MOUSE, RETINA, CEREBROTENDINOUS-XANTHOMATOSIS, OCULODENTODIGITAL DYSPLASIA, ALPHA-V-BETA-5 INTEGRIN

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Citation

Please use this url to cite or link to this publication:

Chicago
Penberthy, Kristen K, Claudia Rival, Laura S Shankman, Michael H Raymond, Jianye Zhang, Justin SA Perry, Chang Sup Lee, et al. 2017. “Context-dependent Compensation Among Phosphatidylserine-recognition Receptors.” Scientific Reports 7.
APA
Penberthy, K. K., Rival, C., Shankman, L. S., Raymond, M. H., Zhang, J., Perry, J. S., Lee, C. S., et al. (2017). Context-dependent compensation among phosphatidylserine-recognition receptors. SCIENTIFIC REPORTS, 7.
Vancouver
1.
Penberthy KK, Rival C, Shankman LS, Raymond MH, Zhang J, Perry JS, et al. Context-dependent compensation among phosphatidylserine-recognition receptors. SCIENTIFIC REPORTS. 2017;7.
MLA
Penberthy, Kristen K, Claudia Rival, Laura S Shankman, et al. “Context-dependent Compensation Among Phosphatidylserine-recognition Receptors.” SCIENTIFIC REPORTS 7 (2017): n. pag. Print.
@article{8538838,
  abstract     = {Phagocytes express multiple phosphatidylserine (PtdSer) receptors that recognize apoptotic cells. It is unknown whether these receptors are interchangeable or if they play unique roles during cell clearance. Loss of the PtdSer receptor Mertk is associated with apoptotic corpse accumulation in the testes and degeneration of photoreceptors in the eye. Both phenotypes are linked to impaired phagocytosis by specialized phagocytes: Sertoli cells and the retinal pigmented epithelium (RPE). Here, we overexpressed the PtdSer receptor BAI1 in mice lacking MerTK (Mertk(-/-) Bai1(Tg)) to evaluate PtdSer receptor compensation in vivo. While Bai1 overexpression rescues clearance of apoptotic germ cells in the testes of Mertk(-/-) mice it fails to enhance RPE phagocytosis or prevent photoreceptor degeneration. To determine why MerTK is critical to RPE function, we examined visual cycle intermediates and performed unbiased RNAseq analysis of RPE from Mertk(+/+) and Mertk(-/-) mice. Prior to the onset of photoreceptor degeneration, Mertk(-/-) mice had less accumulation of retinyl esters and dysregulation of a striking array of genes, including genes related to phagocytosis, metabolism, and retinal disease in humans. Collectively, these experiments establish that not all phagocytic receptors are functionally equal, and that compensation among specific engulfment receptors is context and tissue dependent.},
  articleno    = {14623},
  author       = {Penberthy, Kristen K and Rival, Claudia and Shankman, Laura S and Raymond, Michael H and Zhang, Jianye and Perry, Justin SA and Lee, Chang Sup and Han, Claudia Z and Onengut-Gumuscu, Suna and Palczewski, Krzysztof and Lysiak, Jeffrey J and Ravichandran, Kodi},
  issn         = {2045-2322},
  journal      = {SCIENTIFIC REPORTS},
  keyword      = {PIGMENT EPITHELIAL-CELLS,CARBONIC-ANHYDRASE-IV,APOPTOTIC CELLS,RETINITIS-PIGMENTOSA,PATHOLOGICAL MYOPIA,TYROSINE KINASE,MOUSE,RETINA,CEREBROTENDINOUS-XANTHOMATOSIS,OCULODENTODIGITAL DYSPLASIA,ALPHA-V-BETA-5 INTEGRIN},
  language     = {eng},
  pages        = {14},
  title        = {Context-dependent compensation among phosphatidylserine-recognition receptors},
  url          = {http://dx.doi.org/10.1038/s41598-017-15191-1},
  volume       = {7},
  year         = {2017},
}

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