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

Nat Commun. 2015 Jan 7:6:5717. doi: 10.1038/ncomms6717.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amino Acid Motifs / genetics*
  • Amino Acid Sequence
  • Animals
  • Animals, Genetically Modified
  • Apoptosis
  • Base Sequence
  • Blotting, Western
  • Caenorhabditis elegans / genetics*
  • Caenorhabditis elegans Proteins / chemistry*
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism*
  • Cloning, Molecular
  • DNA Primers / genetics
  • Enzyme-Linked Immunosorbent Assay
  • Fluorescence
  • Germ Cells
  • Green Fluorescent Proteins
  • Immunoprecipitation
  • Models, Molecular*
  • Molecular Sequence Data
  • Polymerase Chain Reaction
  • Receptors, Cell Surface / chemistry*
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / metabolism*
  • Sequence Analysis, DNA
  • Time-Lapse Imaging
  • Ultraviolet Rays

Substances

  • Caenorhabditis elegans Proteins
  • DNA Primers
  • Psr-1 protein, C elegans
  • Receptors, Cell Surface
  • Green Fluorescent Proteins