Calcium binding proteins regulation

A Calcium-Binding Protein Regulates Fusion of Synaptic Vesicles with the Plasma Membrane... 

Calmodulin 16 4Ca Calcium-binding protein regulates a number of cellular functions... 

Sorcin (soluble resistance-related calcium binding protein) was isolated from multidrug-resistant cells and is expressed in a few mammalian tissues such as skeletal muscle, heart, and brain. In the heart, sorcin interacts with the ryanodine receptor and L-type Ca2+-channels regulating excitation in contraction coupling. 

Small ubiquitous calcium-binding protein. Calmodulin binds and regulates the activity of many protein targets involved in cellular signal transduction pathways mediated by calcium. Calmodulin is ranked among the most conserved proteins and plays a key role in many cellular processes. 

It has been shown that the activity of NO synthases is regulated by cofactors calcium binding protein calmodulin and tetrahydrobiopterin (H4B). Abu-Soud et al. [149] have studied the effect of H4B on the activity of neuronal nNOS I, using the isolated heme-containing oxygenase domain nNOSoxy. It was found that nNOSoxy rapidly formed an oxygenated complex in the reaction with dioxygen, which dissociated to produce superoxide (Reaction (6)) ... 

Calmodulin, a calcium binding protein, is involved in Ca2+-dependent regulation of several synaptic functions of the brain synthesis, uptake and release of neurotransmitters, protein phosphorylation and Ca+2 transport. It reacts with TET, TMT and TBT which then inactivates enzymes like Ca+2-ATPase and phosphodiesterase. In vitro studies indicated TBT was greater at inhibiting calmodulin activity than TET and TMT, whereas in vivo the order was TET > TMT > TBT. This may be due to the greater detoxification of TBT (66%) in the liver before moving to other organs30,31. 

The mechanism of action of the vitamin D metabolites remains under active investigation. However, calcitriol is well established as the most potent agent with respect to stimulation of intestinal calcium and phosphate transport and bone resorption. Calcitriol appears to act on the intestine both by induction of new protein synthesis (eg, calcium-binding protein and TRPV6, an intestinal calcium channel) and by modulation of calcium flux across the brush border and basolateral membranes by a means that does not require new protein synthesis. The molecular action of calcitriol on bone has received less attention. However, like PTH, calcitriol can induce RANK ligand in osteoblasts and proteins such as osteocalcin, which may regulate the mineralization process. The metabolites 25(OH)D and 24,25(OH)2D are far less... 

Eue I, Sorg C. 2001. Arachidonic acid specifically regulates binding of S100A8/9, a heterodimer complex of the S100 class of calcium binding proteins, to human microvascular endothelial cells. Atherosclerosis 154(2) 505—508. 

Overall, the regulation of presynaptic calcium channels by different types of calcium binding proteins may provide for mechanisms by which neurons can fine tune the amount of calcium entering presynaptic nerve terminals, shift the relative contributions of N-type and P/Q-type channels to calcium entry, and thus regulate the amount of neurotransmitter that can be released from the synapse. 

The entry of calcium into neurons via presynaptic calcium channels is a key step in evoked neurotransmitter release. Compromised calcium channel function can lead to severe neurological consequences, and yet the pharmacological inhibition of specific calcium channel subtypes can be beneficial in the treatment of conditions such as neuropathic pain. Because of the importance of these channels, neurons have evolved complex means for regulating calcium channel activity, including activation of second messenger pathways by G protein coupled receptors and feedback inhibition by calcium binding proteins. By these means, neurons are able to maintain the fine balance of cytoplasmic calcium levels that is required for optimal neurotransmitter release. 

Few AP, Lautermilch NJ, Westenbroek RE, Scheuer T, Catterall WA (2005) Differential regulation of CaV2.1 channels by calcium-binding protein 1 and visinin-like protein-2 requires N-terminal myristoylation. J Neurosci 25 7071-80... 

A calcium regulated enzyme or protein could be considered as the third type of calcium binding protein. The calcium regulated enzyme is contrasted to the target protein of the calcium dependent regulatory protein in that the calcium regulated enzymes are capable of binding calcium directly and do not require additional proteins to confer calcium sensitivity. An example of this type of calcium receptor is the protein kinase C [8]. 

The first class of membranous calcium binding proteins are represented by those proteins involved in the generation and modulation of the calcium signal (Table III). The calcium signal is regulated by the uptake and release of calcium across the three major membrane systems which bound the cytoplasm (the plasma membrane, the... 

Phosphorylase kinase is one of the best characterized enzyme systems to illustrate the role of calcium ions in regulation of intermediary metabolism. Phosphorylase kinase is composed of four different subunits termed a (Mr 145000), /3 (MT 128000), y (A/r 45000) and 5 (Mr 17000) and has the structure (a/3y8)A [106]. Only one of its four subunits actually catalyses the phosphorylation reaction the other three subunits are regulatory and enable the enzyme complex to be activated both by calcium and cyclic AMP. The y subunit carries the catalytic activity the 8 subunit is the calcium binding protein calmodulin and is responsible for the calcium dependence of the enzyme. The a and /3 subunits are the targets for cyclic-AMP mediated regulation, both being phosphorylated by the cyclic-AMP dependent protein kinase. Calmodulin appears to interact with phosphorylase kinase in a different manner from other enzymes, since it is an integral component of the enzyme. Phosphorylase kinase has an absolute requirement for calcium, and is inactive in its absence. 

---