Annexin-A5: a protein that promotes cell membrane repair

Alain Brisson and its team from the IECB demonstrate in a paper released on April 5 in Nature Communications that Annexine-A5 plays a central role in the cell membrane repair machinery.

This figure compares the behavior of two cells, one that expresses Annexin-A5 (A) and one that does not express Annexin-A5 (B), when their cell membranes are damaged by laser irradiation (the damaged area is indicated by a red arrow). In the case of Annexin-A5 expressing cells, their membranes repair rapidly and spontaneously, while in Annexin-A5 deficient cells, their membranes do not repair, which leads to cell death. (pictures obtained by Anthony Bouter with equipments from the BIC).

Eukaryotic cells, such as the ones from the heart, muscle, skin or the intestine, are submitted to considerable mechanical tension, which result frequently in cell membrane disruptions. Without rapid resealing of the plasma membrane, the cell dies. Several muscular diseases originate from defects of the cell membrane repair machinery.

For more than 20 years, Professor Alain Brisson (CBMN 5248) has been working on Annexin-A5, a protein that binds to membranes and self-assembles into two-dimensional (2D) arrays upon calcium activation. In their last paper, Alain Brisson team unveils the biological function of Annexin-A5: this protein plays a central role in the cell membrane repair machinery.

His team first induced membrane damage via laser irradiation in cells that express Annexin-A5 and in deficient cells in which the Anxa5 gene has been deleted. They found that cells lacking Annexin-A5 present a defect in their cell membrane repair machinery, and that the addition of Annexin-A5 restored the repair ability of these cells.

Then, the behavior of Annexin-A5 mutants that lack the ability to form 2D arrays, was put under scrutiny. They observed that, while these mutant proteins were binding to the sites of membrane injury, they were unable to promote membrane resealing.

This work shows that Annexin-A5 promotes cell membrane repair through the formation of 2D arrays at the sites of membrane rupture by preventing the expansion of the tear and facilitating membrane resealing.

Such a discovery opens new perspectives in the field of annexins and membrane repair research, which may lead to therapeutic applications.

Anthony Bouter, Céline Gounou, Rémi Bérat, Sisareuth Tan, Bernard Gallois, Thierry Granier, Béatrice Langlois d'Estaintot, Ernst Pöschl, Bent Brachvogel & Alain R. Brisson (2011) Annexin-A5 assembled into two-dimensional arrays promotes cell membrane repair, Nature Communications, Vol. 2, 270, DOI:doi:10.1038/ncomms1270