Context-dependent compensation among phosphatidylserine-recognition receptors

Kristen K. Penberthy, Claudia Rival, Laura S. Shankman, Michael H. Raymond, Jianye Zhang, Justin S.A. Perry, Chang Sup Lee, Claudia Z. Han, Suna Onengut-Gumuscu, Krzysztof Palczewski, Jeffrey J. Lysiak, Kodi S. Ravichandran

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

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-/-Bai1Tg) 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.

Original languageEnglish
Article number14623
JournalScientific reports
Volume7
Issue number1
DOIs
StatePublished - Dec 1 2017

Fingerprint

Dive into the research topics of 'Context-dependent compensation among phosphatidylserine-recognition receptors'. Together they form a unique fingerprint.

Cite this