Membrane-binding proteins, calcium-mediated

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). 

OH)2D3-mediated phosphorylation [67]. In the case of PKC, 1,25-(OH)2D3 causes translocation of PKC-/ to the plasma membrane and PKC-a to the nucleus [269-271], Both PKC iso types are calcium-dependent, and l,25-(OH)2D3 does not affect the calcium-independent PKC-f [271], Brown and DeLuca [272] demonstrated that VDR phosphorylation is rapid, occurring within 1 h following treatment of l,25-(OH)2D3 of embryonic chick duodenal organ culture. In addition, phosphorylation occurred before calcium uptake and the 1,25-(OH)2D3-dependent increase in calcium-binding protein mRNA. Proteolytic digestion of the l,25-(OH)2D3-dependent phosphorylation of porcine VDR was mapped and shown to be localized to a 23 Kd fragment of the C-terminal domain [273]. 

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