title: Tailored protection against plasmalemmal injury by annexins with different Ca2+ sensitivities.
abstract: The annexins, a family of Ca(2+)- and lipid-binding proteins, are involved in a range of intracellular processes. Recent findings have implicated annexin A1 in the resealing of plasmalemmal injuries. Here, we demonstrate that another member of the annexin protein family, annexin A6, is also involved in the repair of plasmalemmal lesions induced by a bacterial pore-forming toxin, streptolysin O. An injury-induced elevation in the intracellular concentration of Ca(2+) ([Ca(2+)](i)) triggers plasmalemmal repair. The highly Ca(2+)-sensitive annexin A6 responds faster than annexin A1 to [Ca(2+)](i) elevation. Correspondingly, a limited plasmalemmal injury can be promptly countered by annexin A6 even without the participation of annexin A1. However, its high Ca(2+) sensitivity makes annexin A6 highly amenable to an unproductive binding to the uninjured plasmalemma; during an extensive injury accompanied by a massive elevation in [Ca(2+)](i), its active pool is severely depleted. In contrast, annexin A1 with a much lower Ca(2+) sensitivity is ineffective at the early stages of injury; however, it remains available for the repair even at high [Ca(2+)](i). Our findings highlight the role of the annexins in the process of plasmalemmal repair; a number of annexins with different Ca(2+)-sensitivities provide a cell with the means to react promptly to a limited injury in its early stages and, at the same time, to withstand a sustained injury accompanied by the continuous formation of plasmalemmal lesions.
authors: Department of Cell Biology, Institute of Anatomy, University of Bern, 3012 Bern, Switzerland.
authors: Sarah
authors: S
authors: Potez
authors: Miriam
authors: M
authors: Luginbühl
authors: Katia
authors: K
authors: Monastyrskaya
authors: Andrea
authors: A
authors: Hostettler
authors: Annette
authors: A
authors: Draeger
authors: Eduard B
authors: EB
authors: Babiychuk
mesh_terms: D017305:Annexin A1 / Q000378:metabolism*; D017317:Annexin A6 / Q000378:metabolism*; D001426:Bacterial Proteins / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism* / Q000473:pathology; D057809:HEK293 Cells; D006801:Humans; D013301:Streptolysins / Q000494:pharmacology
chemical_list: D017305:Annexin A1; D017317:Annexin A6; D001426:Bacterial Proteins; D013301:Streptolysins; C025964:streptolysin O; D002118:Calcium