Identification of novel binding partners (annexins) for the cell death signal phosphatidylserine and definition of their recognition motif

Rosenbaum, Sabrina, Kreft, Sandra, Etich, Julia, Frie, Christian, Stermann, Jacek, Grskovic, Ivan, Frey, Benjamin, Mielenz, Dirk, Pöschl, Ernst, Gaipl, Udo, Paulsson, Mats and Brachvogel, Bent (2011) Identification of novel binding partners (annexins) for the cell death signal phosphatidylserine and definition of their recognition motif. Journal of Biological Chemistry, 286 (7). pp. 5708-16. ISSN 0021-9258

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Abstract

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.

Item Type: Article
Uncontrolled Keywords: amino acid motifs,animals,annexins,apoptosis,calcium,evolution, molecular,mice,nih 3t3 cells,phosphatidylserines,protein binding,signal transduction
Faculty \ School: Faculty of Science > School of Biological Sciences
Depositing User: Pure Connector
Date Deposited: 13 Jan 2016 16:00
Last Modified: 22 Apr 2020 00:52
URI: https://ueaeprints.uea.ac.uk/id/eprint/56302
DOI: 10.1074/jbc.M110.193086

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