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Annexin I is an endogenous ligand that mediates apoptotic cell engulfment
Swathi Arur1, Uche E Uche, Karim Rezaul
1Center for Vascular Biology, Department of Physiology, University of Connecticut School of Medicine, 263 Farmington Avenue, Farmington, CT 06030, USA.
Abstract:
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.
Insights
Annexin I acts as a crucial engulfment ligand, moving from the cytosol to the cell surface to aid in the clearance of apoptotic cells. This finding offers new insights into cell removal and inflammatory diseases.
Area of Science:
- Cell Biology
- Molecular Biology
- Immunology
Background:
- Apoptotic cell clearance is vital for tissue homeostasis.
- Dying cells present specific ligands to signal for engulfment.
- Mechanisms of ligand presentation during apoptosis require further elucidation.
Purpose of the Study:
- To identify novel cell surface ligands involved in apoptotic cell engulfment.
- To elucidate the role of annexin I in the clearance of apoptotic cells.
- To investigate the conserved mechanisms of efferocytosis across species.
Main Methods:
- Differential proteomics to identify cell surface proteins on apoptotic cells.
- Immunofluorescence microscopy to track protein localization.
- Gene silencing in Caenorhabditis elegans to assess functional requirements.
Main Results:
- Annexin I was identified as a caspase-dependent engulfment ligand.
- Annexin I translocates from the cytosol to the outer plasma membrane leaflet of apoptotic cells.
- Annexin I is essential for efficient engulfment, colocalizing with phosphatidylserine and influencing phosphatidylserine receptor clustering.
- Downregulation of the annexin homolog in C. elegans impairs apoptotic cell corpse engulfment.
Conclusions:
- Annexin I is a key mediator of apoptotic cell engulfment, acting as a cell surface ligand.
- These findings provide novel mechanistic insights into efferocytosis.
- Dysregulation of annexin I may contribute to chronic inflammatory diseases.