Annexins and Ca handling in the heart

Abstract

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.

Annexin A6 modifies muscular dystrophy by mediating sarcolemmal repair

“…WT 129 fibers were used to avoid endogenous ANXA6N32 protein, and FM4-64 was used to mark membrane damage. Before laser wounding, both ANXA6-GFP and ANXA6N32-GFP localized in a distinct, striated pattern at the Z-band, consistent with the known localization of endogenous annexin A6 (21) (Fig. 4A).…”

“…The annexins are a family of calcium-dependent phospholipid binding proteins (21). Annexins typically contain four annexin repeats with the exception of ANXA6, which contains eight annexin repeats (Fig.…”

Differentiation of the bovine dominant follicle from the cohort upregulates mRNA expression for new tissue development genes

“…Bovine granulosa cell SAGE libraries membrane function, phospholipid transport and cell signalling (Camors et al 2005) have been detected in cells during the G1 to S transition phase of mitosis (Chiang et al 1993). Calmodulin can affect gonadotrophinregulated granulosa cell steroidogenesis through its calcium-binding properties in the laboratory rodents (Carnegie & Tsang 1984, Stocco et al 2002, and macrophage migration inhibitory factor has antioxidant and anti-apoptotic activities (Mitchell & Bucala 2000, Nguyen et al 2003 and may regulate murine follicular development and ovulation (Matsuura et al 2002).…”

Cytosolic Dynamics of Annexin A6 Trigger Feedback Regulation of Hypertrophy via Atrial Natriuretic Peptide in Cardiomyocytes

“…Anxa6, 3 largest member of the annexin family of Ca 2ϩ -and phospholipid-binding proteins, is a major myocardial annexin (5). It is ubiquitously expressed and associated with a variety of physiological functions.…”