Annexin VI regulation of cardiac function.

Annexins are a family of membrane binding proteins that are characterized by a hypervariable amino terminus followed by a series of highly conserved Ca2+-phospholipid binding domains. Annexins function by binding to anionic phospholipid surfaces in a Ca2+-dependent manner. They self-associate to form trimers which further assemble into sheets that cover the membrane surface and alter properties such as fluidity and permeability. This submembranous skeleton alters integral protein functions such as ion transport properties and shields the surface from phospholipid binding proteins such as phospholipases and protein kinase C. Transgenic mouse hearts overexpressing wild type annexin VI (AnxVI673), a dominant-negative truncated annexin VI (residues 1-129, Anx129) and an annexin VI-null mouse (AnxVI-/-) have implicated the protein as a regulator of intracellular Ca2+ homeostasis which affects cardiac function.