Calcium pumps regulation

Zamoon J, Nitu F, Karim C, Thomas DD, Veglia G (2005) Mapping the interaction surface of a membrane protein unveiling the conformational switch of phospholamban in calcium pump regulation. Proc Natl Acad Sci USA 102 4747 752... 

Axelband F, Assungao-Miranda I, de Paula IR, Ferrao FM, Dias J, Miranda A, Miranda F, Lara LS, Vieyra A. (2009) Ang-(3 ) suppresses inhibition of renal plasma membrane calcium pump by Ang II. Regul Pept 155 81-90. 

Activity is modulated by other proteins present in the membrane. These include a glycoprotein (MW 53 000) which stimulates ATPase activity 138 a 60 000 molecular weight protein, which is phosphorylated in a calmodulin-dependent fashion, affects accumulation of calcium 139 while the activity of the enzyme is affected by an endogenous kinase and phosphatase which phosphorylates and dephosphorylates the protein.140 Phospholamban is a proteolipid (MW 22 000) in cardiac SR which undergoes both cyclic AMP-dependent and calcium-calmodulin-dependent phosphorylation,141 but at different sites. All these proteins are probably involved in regulating the activity of the calcium pump. 

Schuh, K., Uldrijan, S., Telkamp, M., Rothlein, N., Neyses, L., 2001, The plasmamembrane calmodulin-dependent calcium pump a major regulator of nitric oxide synthase I. J Cell Biol 155, 201-205. 

Garrahan, P.J. Rega, A.F. (1990). Plasma Membrane Calcium Pump In Intracellular Calcium Regulation (Bronner, F., ed.), pp. 271-303, Alan R. Liss, Inc., New York. 

Carafoli, E. Chiesi, M. (1992). Calcium pumps in the plasma and intracellular membranes. Curr. Top. Cell. Regul. 32,209-241. 

This obvious dependence on extracellular calcium is somewhat unexpected because (1) the sustained enhancement of calcium influx rate is adequately balanced by an increase in calcium efflux rate so that (2) the calcium concentration in the bulk cytosol is maintained near the basal value. This apparent paradox may be resolved by a model [54] which postulates that during the sustained phase of cellular response the high rate of calcium cycling across the plasma membrane raises the calcium concentration in a region just below the plasma membrane, often called the submembrane domain (see Rasmussen and Barrett, Chapter 4). Because the elevated calcium level in this domain is not conducted into the bulk cytosol, it cannot activate calcium-dependent response elements in the cytosol. Rather it regulates the activity of calcium-sensitive, plasma membrane-associated enzymes such as the calcium pump and PKC, the previously described phospholipid-dependent, calcium-activated protein kinase. 

Aluminum in micromolar concentrations was found to inhibit calcium pumping in endoplasmic reticulum. The Ca2+ ATPase activity of rat brain and cerebellum was remarkably reduced and mitochondria showed increased Ca2+ release in the presence of exactly estimated 50 pmol L-1 Al3+ [67]. Aluminum was found to be an important disrupter of intracellular calcium homeostasis, interfering also with the mitochondrial Ca2+ pump, as well as activating an Na+-K+ ATPase - the antiport mechanism of ion exchange in the plasma membrane, which regulates the Ca2+-Na+ antiporter exchange [67]. 

The recent discoveries of PHB and polyP in a human calcium pump and bacterial potassium channel suggest that the naked PHB/polyP complexes found in bacteria are progenitors of protein ion transporters. The process by which protein channels and pumps may have evolved from PHB/polyP complexes is unknown however, one may surmise that over time proteins surrounded the complexes to support and regulate their activity. At first, the association may have been nonco-valent, but subsequently PHB may have become tethered to the protein by a covalent bond. By this view, many of the channels and pumps of prokaryotes and eukaryotes may be supramolecular structures in which protein, polyP, and PHB join together for efficient regulation of transmembrane ion transport. 

Calcium ions are also transported into the cell by a pump, which is a Ca +-dependent ATPase. This pump is necessary because the calcium ion concentration is four orders of magnitude higher outside than inside living cells. Calmodulin regulates the level of calcium ions and hence the calcimn pump. When the calcium concentration decreases, calcium is dissociated from calmodulin and the calcium pump is inactivated. The structure of such a pump from the sarcoplasmic reticulum is reported at 8 A resolution. This pump couples ATP hydrolysis with cation transport. The protein contains 10 transmembrane helices. A distinct cavity was located that led to the putative calcium-binding site, suggesting a path for a calcium passage. 

Phospholamban is a homopentameric membrane protein involved in muscle contraction through regulation of the calcium pump in cardiac muscle cells. The stmcture of the unphospho-rylated protein solved in DPC micelles reveals a symmetric pentamer of phospholamban monomers (Fig. 2g) stabilized by leucine/isoleucine zipper motifs along the transmembrane domains (51). Notably, another stmcture was produced for phospholamban (Fig. 2h) that used a variant of the traditional simulated annealing and molecular dynamics protocol that reduced the chances of entrapment in local minima (52). 

Carafoli, E. (1984). Calmodulin-sensitive calcium-pumping ATPase of plasma membranes Isolation, reconstitution and regulation. Fed. Proc. 43, 3005-3010. 

Pozzan T, Rizzuto R, Volpe P, Meldolesi J (1994) Molecular and cellular physiology of intracellular calcium stores. Physiol Rev 74 595-636 Raeymakers L, Wuytack F (1996) Calcium pumps. In Barany M (ed) Biochemistry of smooth muscle contraction. Academic Press, San Diego, pp 241-253 Rembold CM (1990) Modulation of the [Ca " ] sensitivity of myosin phosphorylation in intact swine arterial smooth muscle. J Physiol 429 77-94 Rembold CM, Weaver BA (1990) [Ca ], not diacylglycerol, is the primary regulator of sustained swine arterial smooth muscle contraction. Hypertension 15 692-698 Shimada T, Somlyo AP (1992) Modulation of voltage-dependent Ca channel current by arachidonic acid and other long-chain fatty acids in rabbit intestinal smooth muscle. J Gen Physiol 100 27-44... 

Cells constantly, either actively or passively, transport chemicals across the plasma membrane and communicate with surrounding cells, generating chemical diffusion gradients around them. Measurement of such activities within gradients enables a better understanding of the cellular transport mechanisms. For example, calcium is regulated to nanomolar values in the cytosol by a complex interaction of cellular and plasma membrane pumps, reporters, channel activity, regional sequestration, and chemical... 

In addition to the sodium pump, there is a calcium pump which plays an important part in the regulation of muscular contraction. Calcium ions released during the passage of an impulse act as an intermediary between the nerve and the muscle. Although there is no doubt that these cations are actively transported, the concentrations of Cl" and HC03" within the cell seem to depend on ordinary electrochemical phenomena. 

Sarcoplasmic calcium ATPase this enzyme utilizes the energy gained from hydrolysis of ATP to pump calcium from the cytosol into the stores of the sarcoplasmic reticulum. Its activity is negatively regulated by the closely associated protein phospholamban, and this inhibition is relieved upon phosphorylation of phospholamban by protein kinase A (PKA). 

The sarcolemmal Na/K pump plays an imp>ortant, although indirect role in the regulation of cellular calcium homeostasis. The transmembrane Na gradient is maintained by the activity of the Na/K pump and the thermodynamic energy of this gradient in turn drives the Na/Ca exchange mechanism (Sheu and Fozzard, 1982 Barry and Bridge, 1993). Thus, the intracellular Ca concentration is closely related to intracellular Na and the activity of the Na/K pump (Bers and Ellis, 1982). 

The binding of calcium ion to calmodulin, a major biochemical regulator of ion pumps and receptors, occurs on a time scale about a thousand times shorter than that observed for RNA conformational change. This Ca2+-calmodulin binding, which can be followed successfully by nuclear magnetic resonance (NMR), occurs in about ten milliseconds. 

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