Annexin I is an endogenous ligand that mediates apoptotic cell engulfment.
Engulfment of apoptotic cells requires presentation of new cell surface ligands by the dying cells. Using a differential proteomics technology, we identify that annexin I is a caspase-dependent engulfment ligand; it is recruited from the cytosol and exported to the outer plasma membrane leaflet, colocalizes with phosphatidylserine, and is required for efficient clearance of apoptotic cells. Furthermore, phosphatidylserine receptor (PSR) clustering around apoptotic cells indicates a requirement for annexin I. In the nematode Caenorhabditis elegans, downregulation of the annexin homolog prevents efficient engulfment of pharyngeal cell corpses. These results provide novel mechanistic insights into how apoptotic cells are removed and may explain a pathogenic mechanism of chronic inflammatory diseases where annexin I autoantibodies have been described.
Arur
Swathi
S
Center for Vascular Biology, Department of Physiology, University of Connecticut School of Medicine, 263 Farmington Avenue, Farmington, CT 06030, USA.
Uche
Uche E
UE
Rezaul
Karim
K
Fong
Michael
M
Scranton
Victoria
V
Cowan
Ann E
AE
Mohler
William
W
Han
David K
DK
D000818:Animals; D017305:Annexin A1 / Q000378:metabolism*; D017302:Annexins / Q000378:metabolism; D017209:Apoptosis / Q000502:physiology*; D017173:Caenorhabditis elegans / Q000166:cytology / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins; D020013:Calcium Signaling / Q000502:physiology; D020169:Caspases / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism*; D021961:Cell Membrane Structures / Q000378:metabolism; D015536:Down-Regulation / Q000502:physiology; D005057:Eukaryotic Cells / Q000166:cytology / Q000378:metabolism*; D015801:Helminth Proteins / Q000378:metabolism; D006801:Humans; D056484:Jumonji Domain-Containing Histone Demethylases; D019169:Jurkat Cells; D008024:Ligands; D008565:Membrane Proteins / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism; D010587:Phagocytosis / Q000502:physiology*; D021381:Protein Transport / Q000502:physiology; D011956:Receptors, Cell Surface / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D015854:Up-Regulation / Q000502:physiology
D017305:Annexin A1; D017302:Annexins; D029742:Caenorhabditis elegans Proteins; D015801:Helminth Proteins; D008024:Ligands; D008565:Membrane Proteins; C098890:Nex-1 protein, C elegans; D010446:Peptide Fragments; D011956:Receptors, Cell Surface; C408123:phosphatidylserine receptor; C498707:JMJD6 protein, human; D056484:Jumonji Domain-Containing Histone Demethylases; D020169:Caspases