A lysine-rich motif in the phosphatidylserine receptor PSR-1 mediates recognition and removal of apoptotic cells

作者:Yang Hengwen; Chen Yu Zen; Zhang Yi; Wang Xiaohui; Zhao Xiang; Godfroy James I III; Liang Qian; Zhang Man; Zhang Tianying; Yuan Quan; Royal Mary Ann; Driscoll Monica; Xia Ning Shao; Yin Hang; Xue Ding*
来源:Nature Communications, 2015, 6(1): 5717.
DOI:10.1038/ncomms6717

摘要

The conserved phosphatidylserine receptor (PSR) was first identified as a receptor for phosphatidylserine, an 'eat-me' signal exposed by apoptotic cells. However, several studies suggest that PSR may also act as an arginine demethylase, a lysyl hydroxylase, or an RNA-binding protein through its N-terminal JmjC domain. How PSR might execute drastically different biochemical activities, and whether they are physiologically significant, remain unclear. Here we report that a lysine-rich motif in the extracellular domain of PSR-1, the Caenorhabditis elegans PSR, mediates specific phosphatidylserine binding in vitro and clearance of apoptotic cells in vivo. This motif also mediates phosphatidylserine-induced oligomerization of PSR-1, suggesting a mechanism by which PSR-1 activates phagocytosis. Mutations in the phosphatidylserine-binding motif, but not in its Fe(II) binding site critical for the JmjC activity, abolish PSR-1 phagocytic function. Moreover, PSR-1 enriches and clusters around apoptotic cells during apoptosis. These results establish that PSR-1 is a conserved, phosphatidylserine-recognizing phagocyte receptor.