title: A lysine-rich motif in the phosphatidylserine receptor PSR-1 mediates recognition and removal of apoptotic cells.
abstract: 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.
authors.affiliation: Department of Molecular, Cellular and Developmental Biology, University of Colorado, Boulder, Colorado 80309, USA.
authors.forename: Hengwen
authors.initials: H
authors.lastname: Yang
authors.affiliation: Department of Molecular, Cellular and Developmental Biology, University of Colorado, Boulder, Colorado 80309, USA.
authors.forename: Yu-Zen
authors.initials: YZ
authors.lastname: Chen
authors.affiliation: School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Chemistry &Biochemistry and BioFrontiers Institute, University of Colorado, Boulder, Colorado 80309, USA.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Wang
authors.affiliation: School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Department of Chemistry &Biochemistry and BioFrontiers Institute, University of Colorado, Boulder, Colorado 80309, USA.
authors.forename: James I
authors.initials: JI
authors.lastname: Godfroy
authors.affiliation: School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Liang
authors.affiliation: School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Man
authors.initials: M
authors.lastname: Zhang
authors.affiliation: National Institute of Diagnostics and Vaccine Development in Infectious Diseases, Xiamen University, Xiamen 361102, China.
authors.forename: Tianying
authors.initials: T
authors.lastname: Zhang
authors.affiliation: National Institute of Diagnostics and Vaccine Development in Infectious Diseases, Xiamen University, Xiamen 361102, China.
authors.forename: Quan
authors.initials: Q
authors.lastname: Yuan
authors.affiliation: Department of Molecular Biology and Biochemistry, Rutgers, The State University of New Jersey, Piscataway, New Jersey 08854, USA.
authors.forename: Mary
authors.initials: M
authors.lastname: Ann Royal
authors.affiliation: Department of Molecular Biology and Biochemistry, Rutgers, The State University of New Jersey, Piscataway, New Jersey 08854, USA.
authors.forename: Monica
authors.initials: M
authors.lastname: Driscoll
authors.affiliation: National Institute of Diagnostics and Vaccine Development in Infectious Diseases, Xiamen University, Xiamen 361102, China.
authors.forename: Ning-Shao
authors.initials: NS
authors.lastname: Xia
authors.affiliation: 1] Department of Chemistry &Biochemistry and BioFrontiers Institute, University of Colorado, Boulder, Colorado 80309, USA [2] Center of Basic Molecular Science and Department of Chemistry, Tsinghua University, Beijing 100082, China.
authors.forename: Hang
authors.initials: H
authors.lastname: Yin
authors.affiliation: 1] Department of Molecular, Cellular and Developmental Biology, University of Colorado, Boulder, Colorado 80309, USA [2] School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Ding
authors.initials: D
authors.lastname: Xue
mesh_terms: D020816:Amino Acid Motifs / Q000235:genetics*; D000595:Amino Acid Sequence; D000818:Animals; D030801:Animals, Genetically Modified; D017209:Apoptosis; D001483:Base Sequence; D015153:Blotting, Western; D017173:Caenorhabditis elegans / Q000235:genetics*; D029742:Caenorhabditis elegans Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D003001:Cloning, Molecular; D017931:DNA Primers / Q000235:genetics; D004797:Enzyme-Linked Immunosorbent Assay; D005453:Fluorescence; D005854:Germ Cells; D049452:Green Fluorescent Proteins; D047468:Immunoprecipitation; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011956:Receptors, Cell Surface / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D017422:Sequence Analysis, DNA; D059008:Time-Lapse Imaging; D014466:Ultraviolet Rays
chemical_list: D029742:Caenorhabditis elegans Proteins; D017931:DNA Primers; C479694:Psr-1 protein, C elegans; D011956:Receptors, Cell Surface; D049452:Green Fluorescent Proteins