Identification and clearance of apoptotic cells prevents the release of harmful 
cell contents thereby suppressing inflammation and autoimmune reactions. Highly 
conserved annexins may modulate the phagocytic cell removal by acting as 
bridging molecules to phosphatidylserine, a characteristic phagocytosis signal 
of dying cells. In this study five members of the structurally and functionally 
related annexin family were characterized for their capacity to interact with 
phosphatidylserine and dying cells. The results showed that AnxA3, AnxA4, 
AnxA13, and the already described interaction partner AnxA5 can bind to 
phosphatidylserine and apoptotic cells, whereas AnxA8 lacks this ability. 
Sequence alignment experiments located the essential amino residues for the 
recognition of surface exposed phosphatidylserine within the calcium binding 
motifs common to all annexins. These amino acid residues were missing in the 
evolutionary young AnxA8 and when they were reintroduced by site directed 
mutagenesis AnxA8 gains the capability to interact with phosphatidylserine 
containing liposomes and apoptotic cells. By defining the evolutionary conserved 
amino acid residues mediating phosphatidylserine binding of annexins we show 
that the recognition of dying cells represent a common feature of most annexins. 
Hence, the individual annexin repertoire bound to the cell surface of dying 
cells may fulfil opsonin-like function in cell death recognition.