Calcium-mediated membrane-binding

III. Calcium-Mediated Membrane-Binding Proteins A. Introduction... 

Calcium-mediated membrane binding of proteins occurs both inside cells and outside. At first one might think that these events should be very different in these two different environments, with calcium concentrations in (jlM and mM, respectively. It is, however, not necessarily so. 

In the kiss-and-run mode exocytosis and endocytosis are directly coupled to each other, while in the case of classical complete vesicle fusion, exocytosis and slow clathrin-mediated endocytosis are timely and spatially separated. However, it appears that also in the latter case exocytosis and endocytosis occur coordinated, as both are stimulated by an increase of the cytoplasmic calcium concentration. It has been shown that after calcium entry the enzyme phospho-inositol-5 kinase Iy, which is enriched in the synapse, catalyzes the synthesis of phosphatidylinos-itol (4,5)-bisphosphate and that this mechanism is important for synaptic vesicle trafficking (Di Paolo et al. 2004). As many proteins involved in clathrin-mediated endocytosis are recruited to the plasma membrane by binding to phosphatidylinosi-tol (4,5)-bisphosphate (e.g., amphiphysin, dynamin, epsin, AP-180, and AP-2) it is attractive to speculate that elevated levels of calcium mediate the recruitment of en-docytic proteins to the plasma membrane by this mechanism. The increased level of phosphatidylinositol (4,5)-bisphosphate could be in part degraded by synaptojanin that thereby initiates the disassembly of the clathrin coat. Hence, calcium-induced transient increases in the level of phosphatidylinositol (4,5)-bisphosphate appear to play a central role for coupling exocytosis to clathrin-mediated endocytosis. In addition, it has been demonstrated that calcium also leads to the dephosphorylation of endocytic proteins as amphiphysin, dynamin, and synaptojanin, which in vitro is important for efficient coat assembly (Cousin and Robinson 2001). 

Once released within the lung, the leukotrienes are hypothesized to induce bronchoconstriction of airway smooth muscle through a receptor-mediated process, Binding sites specific for the leukotrienes have been identified in human lung parenchyma (Nicosia et al., 1984) and are believed to represent receptors on the plasma membrane of airway smooth-muscle cells. The interaction of the leukotrienes with a receptor is then hypothesized to induce the release of intracellular calcium in the smooth-muscle cell (Welchman et al., 1983). As with mast cells, intracellular events within the smooth-muscle cells are believed to be modulated via the calcium-binding protein... 

The first membrane binding is mediated via multiple calcium binding sites located at the convex side of the disk-shaped annexin core. The N-terminus of the protein that is presumed to harbor the second membrane binding site is buried in the core domain in the absence of Cd , and is supposed to get exposed to the aqueous phase if annexin Al binds to a membrane in the presence of calcium ions (see Fig. 6) [42]. To verify this hypothesis, again SSMs are well suited, since they allow separation of the first and second membrane binding events. N-terminal truncated annexin Al an-... 

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