Calcium endoplasmic reticulum, mobilization

Inositol triphosphate is water soluble and therefore diffuses into the cytoplasm, where it mobilizes calcium from its stores in microsomes or the endoplasmic reticulum. The Ca ions then activate Ca-dependent kinases (like troponin C in muscle) directly or bind to the ubiquitous Ca-binding protein calmodulin, which activates calmodulin-dependent kinases. These kinases, in turn, phosphorylate cell-specific enzymes. 

Figure 6.12 The cellular toxicity of TBT caused by damage to the thiols of the Ca2+ pump. This leads to dramatic mobilization of calcium from the ER. The filled circles represent ATP-dependent Ca2+ transporters. Abbreviations TBT, tri-n-butyltin chloride ER, endoplasmic reticulum.

O Rourke, F. A., LaPlante, J. M. and Feinstein, M. B., 2003, Antisense-mediated loss of calcium homoeostasis endoplasmic reticulum protein (CHERP ERPROT213-21) impairs Ca2+ mobilization, nuclear factor of activated T-cells (NFAT) activation and cell proliferation in Jurkat T-lymphocytes. Biochem J 373, 133-43. 

IP3 mobilizes Ca2+ from intra- or extracellular stores. The interior of a cell is kept very low in Ca2+ ions, at a concentration less than 10-9 M., while the outside [Ca2+] is about 10-3 M. This million-fold concentration gradient is the result of cellular calcium-dependent ATPase protein. Ca-ATPase uses up to a third of the ATP synthesized by a cell to maintain the concentration gradient. The stores of Ca2+ available for use inside the cell are found primarily in the endoplasmic reticulum. A large store of Ca2+ exists in the mitochondrial matrix, but this seems to be a final dumping ground —in other words, calcium ions in the mitochondria don t come into the cytoplasm. 

Many oncogenes such as ras, src, sis, fms, and fes enhance cellular PI turnover. Phosphatidyl breakdown by phospholipase C generates two second messengers, diacyIglycerol and inositol trisphosphate. The formed directly activates protein kinase C, and the latter binds to the receptor on endoplasmic reticulum to mobilize calcium ions. Therefore, we screened culture filtrates of microorganisms for inhibitors of PI turnover and thus isolated psi-tectorigenin (Fig. 11, ref. 23). ... 

Hydrolysis of PIP2 into IP3 and diacylglycerol (DAG) results in a cascade of intracellular responses, including mobilization of intracellular calcium, sequestered in golgi and endoplasmic reticulum [67,81]. Release of calcium transients is due to interaction with formed IP3 and an IPg-specific receptor (which is Ca -sensitive). In addition, Ca" VCalmodulin and DAG act in conjunction to activate protein kinase C (PKC) which will phosphorylate a number of proteins. 

The anthranilamide, DP-012, stimulates a rise in [Ce ]i under conditions of Ca -free saline similar to that observed with standard saline, indicating that this chemistry mobilizes calcium from internal calcium stores rather than through external entry via voltage-gated Ca channels. Three possible targets are involved in release of internal calcium stores, inositol trisphosphate receptors (IP3RS), ryanodine receptors (RyRs), and sarco-endoplasmic reticulum ATPase (SERCA). These P. americana neurons possess fimctional ryanodine receptors. 

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