Annexins and Ca2+ handling in the heart.
Annexins are a family of 13 proteins known to bind phospholipids (PL) in a Ca(2+)-dependent way. They are ubiquitous proteins and share a similar structure characterized by a conserved C-terminal domain with Ca(2+) binding sites and a variable N-terminal domain. Depending on Ca(2+) concentration, they have been reported to participate in a variety of membrane-related events such as exocytosis, endocytosis, apoptosis and binding to cytoskeletal proteins. They have also been reported to regulate protein activities. This review will focus on annexins in the heart, and particularly on annexins A2, A5, A6 and A7. Annexin A2 has been found in endothelial cells and reported to play a central role in control of plasmin-mediated processes. Annexin A5 is mainly localized in cardiomyocytes. However, it could be relocated to interstitial tissue in ischemic and failing hearts or it could be externalized and exhibit a proapoptotic effect in cardiomyocytes. Annexin A6 is the most abundant annexin in the heart, and has been localized in various cell types including myocytes. Overexpression of annexin A6 has underlined physiological alterations in contractile mechanics leading to dilated cardiomyopathy, whereas knockout has been found to induce faster changes in Ca(2+) transient and increased contractility, suggesting a negative inotropic role for annexin A6. Annexin A7 is expressed in heart and skeletal muscle. In annexin A7 null mutant mice decreases in the force-frequency relationship were observed in adult cardiomyocytes, consistent with regulation of Ca(2+) handling. In conclusion, while annexin A2 was involved in regulation of fibrin homeostasis, alterations in expression and activity of annexins A5, A6 and A7 have been associated with regulation of Ca(2+) handling in the heart, but the target of each annexin has not yet been identified.
Camors
Emmanuel
E
INSERM U572, IFR Circulation, Hôpital Lariboisière, 41 Bd de la Chapelle, 75475 Paris cedex 10, France.
Monceau
Virginie
V
Charlemagne
Daniéle
D
D000818:Animals; D017302:Annexins / Q000032:analysis / Q000502:physiology*; D002118:Calcium / Q000378:metabolism*; D006333:Heart Failure / Q000378:metabolism; D006801:Humans; D009206:Myocardium / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000378:metabolism
D017302:Annexins; D002118:Calcium