The phosphatidylserine receptor from Hydra is a nuclear protein with potential Fe(II) dependent oxygenase activity.
BACKGROUND
Apoptotic cell death plays an essential part in embryogenesis, development and maintenance of tissue homeostasis in metazoan animals. The culmination of apoptosis in vivo is the phagocytosis of cellular corpses. One morphological characteristic of cells undergoing apoptosis is loss of plasma membrane phospholipid asymmetry and exposure of phosphatidylserine on the outer leaflet. Surface exposure of phosphatidylserine is recognised by a specific receptor (phosphatidylserine receptor, PSR) and is required for phagocytosis of apoptotic cells by macrophages and fibroblasts.


RESULTS
We have cloned the PSR receptor from Hydra in order to investigate its function in this early metazoan. Bioinformatic analysis of the Hydra PSR protein structure revealed the presence of three nuclear localisation signals, an AT-hook like DNA binding motif and a putative 2-oxoglutarate (2OG)-and Fe(II)-dependent oxygenase activity. All of these features are conserved from human PSR to Hydra PSR. Expression of GFP tagged Hydra PSR in hydra cells revealed clear nuclear localisation. Deletion of one of the three NLS sequences strongly diminished nuclear localisation of the protein. Membrane localisation was never detected.


CONCLUSIONS
Our results suggest that Hydra PSR is a nuclear 2-oxoglutarate (2OG)-and Fe(II)-dependent oxygenase. This is in contrast with the proposed function of Hydra PSR as a cell surface receptor involved in the recognition of apoptotic cells displaying phosphatidylserine on their surface. The conservation of the protein from Hydra to human infers that our results also apply to PSR from higher animals.
Cikala
Mihai
M
Department Biologie II, Ludwig-Maximilians-University Munich, Luisenstr, 14 D-80333 Munich, Germany. st2057@zi.biologie.uni-muenchen.de
Alexandrova
Olga
O
David
Charles N
CN
Pröschel
Matthias
M
Stiening
Beate
B
Cramer
Patrick
P
Böttger
Angelika
A
D020816:Amino Acid Motifs / Q000235:genetics; D000818:Animals; D029742:Caenorhabditis elegans Proteins / Q000737:chemistry; D019295:Computational Biology / Q000379:methods; D017124:Conserved Sequence / Q000235:genetics; D029721:Drosophila Proteins / Q000737:chemistry; D019143:Evolution, Molecular; D005296:Ferrous Compounds / Q000378:metabolism*; D049452:Green Fluorescent Proteins; D006801:Humans; D006829:Hydra / Q000201:enzymology*; D056484:Jumonji Domain-Containing Histone Demethylases; D008164:Luminescent Proteins / Q000096:biosynthesis; D051379:Mice; D019913:Nuclear Localization Signals / Q000737:chemistry / Q000235:genetics; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D010105:Oxygenases / Q000737:chemistry / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis
D029742:Caenorhabditis elegans Proteins; D029721:Drosophila Proteins; D005296:Ferrous Compounds; D008164:Luminescent Proteins; D019913:Nuclear Localization Signals; D009687:Nuclear Proteins; C498708:Ptdsr protein, mouse; D011956:Receptors, Cell Surface; D011993:Recombinant Fusion Proteins; C408123:phosphatidylserine receptor; D049452:Green Fluorescent Proteins; D010105:Oxygenases; C498707:JMJD6 protein, human; D056484:Jumonji Domain-Containing Histone Demethylases