Figures & data
Figure 1. Schematic visualization of annexins as regulators of formation of lipid second messengers interfering with the activity of cytosolic phospholipase A2 (PLA2) and other phospholipases, as well as mediators of the activity of various protein and lipid kinases (including proteins kinase C isoforms) playing regulatory roles in different lipid mediated signaling pathways. The scheme illustrates the idea formulated by Dedman and his co-workers (Kaetzel and Dedman Citation1995, Seaton and Dedman Citation1998) suggesting that upon a rise in intracellular [Ca2+]c annexin monomers (depicted in green), bind initially to certain lipid constituents of the inner leaflet of the plasma membrane, preferably to lipid microdomains enriched either in anionic phospholipids (such as phosphatidylserine, phosphatidylinositol or phosphatidylinositol 4,5-bisphosphate) or to cholesterol and sphingomyelin or ceramides (depicted in the figure in various colors). Then, annexins bound to the membranes interact with each other to form larger arrays on the membrane surface and, therefore, prevent the interaction of phospholipases, other lipid hydrolyzing enzymes, as well as protein and lipid kinases, with their substrates at the membrane. Other explanations are in the text. Redrawn from Kaetzel and Dedman (Citation1995), modified. This Figure is reproduced in color in the online version of Molecular Membrane Biology.
![Figure 1. Schematic visualization of annexins as regulators of formation of lipid second messengers interfering with the activity of cytosolic phospholipase A2 (PLA2) and other phospholipases, as well as mediators of the activity of various protein and lipid kinases (including proteins kinase C isoforms) playing regulatory roles in different lipid mediated signaling pathways. The scheme illustrates the idea formulated by Dedman and his co-workers (Kaetzel and Dedman Citation1995, Seaton and Dedman Citation1998) suggesting that upon a rise in intracellular [Ca2+]c annexin monomers (depicted in green), bind initially to certain lipid constituents of the inner leaflet of the plasma membrane, preferably to lipid microdomains enriched either in anionic phospholipids (such as phosphatidylserine, phosphatidylinositol or phosphatidylinositol 4,5-bisphosphate) or to cholesterol and sphingomyelin or ceramides (depicted in the figure in various colors). Then, annexins bound to the membranes interact with each other to form larger arrays on the membrane surface and, therefore, prevent the interaction of phospholipases, other lipid hydrolyzing enzymes, as well as protein and lipid kinases, with their substrates at the membrane. Other explanations are in the text. Redrawn from Kaetzel and Dedman (Citation1995), modified. This Figure is reproduced in color in the online version of Molecular Membrane Biology.](/cms/asset/a7ff65d1-317b-47a2-816b-c6a97f7df4e8/imbc_a_693210_f0001_b.jpg)
Figure 2. The activity of ubiquitous mammalian group IVA cPLA2 (cPLA2α) is tightly regulated by various factors, such as phosphorylation at multiple serine residues, [Ca2+], lipid mediators and various proteins, including annexin A2/S100A10 heterotetramer (AnxA22S100A102). A cPLA2α calcium-dependent binding to the plasma membrane is assured by the presence of an NH2-terminal C2 domain (C2) within the enzyme molecule. According to the mechanism proposed by Cho and his co-workers (Tian et al. Citation2008) upon rise in intracellular [Ca2+] AnxA22S100A102 heterotetramer interacts with cPLA2α (the binding occurs via the hydroxyl group of Ser727 (S727) of cPLA2α that forms hydrogen bonds with S100A10 in the heterotetramer) and thus prevents its binding to the membrane and inhibits the enzyme. Phosphorylation of the Ser727 residue affects the cPLA2α-AnxA22S100A102 interaction, thereby allowing phospholipase activation and subsequent lipid hydrolysis through binding to the membrane. Phosphorylation of another residue of cPLA2α, Ser505 at C2 domain, does not appear to influence the cPLA2α-AnxA22S100A102 interaction. On the Figure the lipid microdomain (pink) enriched in phosphatidylinositol 4,5-bisphosphate, a well known partner molecule for AnxA2, is depicted as a potential membrane target for the heterotetramer. Such domain could be stabilized by cholesterol molecules (Gokhale et al. Citation2005). Other explanations are in the text. Adapted from Tian et al. (Citation2008), with some modifications. This Figure is reproduced in color in the online version of Molecular Membrane Biology.
![Figure 2. The activity of ubiquitous mammalian group IVA cPLA2 (cPLA2α) is tightly regulated by various factors, such as phosphorylation at multiple serine residues, [Ca2+], lipid mediators and various proteins, including annexin A2/S100A10 heterotetramer (AnxA22S100A102). A cPLA2α calcium-dependent binding to the plasma membrane is assured by the presence of an NH2-terminal C2 domain (C2) within the enzyme molecule. According to the mechanism proposed by Cho and his co-workers (Tian et al. Citation2008) upon rise in intracellular [Ca2+] AnxA22S100A102 heterotetramer interacts with cPLA2α (the binding occurs via the hydroxyl group of Ser727 (S727) of cPLA2α that forms hydrogen bonds with S100A10 in the heterotetramer) and thus prevents its binding to the membrane and inhibits the enzyme. Phosphorylation of the Ser727 residue affects the cPLA2α-AnxA22S100A102 interaction, thereby allowing phospholipase activation and subsequent lipid hydrolysis through binding to the membrane. Phosphorylation of another residue of cPLA2α, Ser505 at C2 domain, does not appear to influence the cPLA2α-AnxA22S100A102 interaction. On the Figure the lipid microdomain (pink) enriched in phosphatidylinositol 4,5-bisphosphate, a well known partner molecule for AnxA2, is depicted as a potential membrane target for the heterotetramer. Such domain could be stabilized by cholesterol molecules (Gokhale et al. Citation2005). Other explanations are in the text. Adapted from Tian et al. (Citation2008), with some modifications. This Figure is reproduced in color in the online version of Molecular Membrane Biology.](/cms/asset/18f0d84a-6f06-408f-bbc2-72bb538c28c5/imbc_a_693210_f0002_b.jpg)