Calcium sensors

A second class of neuronal calcium sensors is formed by the guanylate cyclase-activating protein (GCAP). The GCAPs are expressed only in the photoreceptor cells of the retina of vertebrates. Recoverins and GCAPs have antagonistic roles in phototransduction. 

Baba Y Nishida K, Fujii Y Hirano X Hikida M, Kurosaki X Essential function for the calcium sensor SXIMl in mast cell activation and anaphylactic responses. Nat Immunol 2008 9 81-88. 

Use of biochemical and biological information for bioprocesses is also significant to the advancement of BRE. Here, the information on the signal transduction from external Ca was utilized for regulation of ginsenoside biosynthetic pathway of cultured cells of P. notoginseng. A quantitative study on the effects of external calcium and calcium sensors was conducted to... 

Fig. 3. A proposed signal transduction pathway regarding the external Ca effect on ginsenoside Rb synthesis by P. notoginseng cells. Ca signal changes are triggered by external Ca concentrations. The calcium signatures are decoded by calcium sensors, CaM and CDPK. UGRdGT is possibly modulated by the sensors in a direct or indirect (dashed lines) way. Changes of CDPK activity may result from increased synthesis or posttranslational modification of the enzyme (shown as CDPK ).

Structural and functional evidence clearly demonstrates that family C receptors function as dimers, either as homodimers or as heterodimers. The metabotropic glutamate receptors and the calcium sensors, as discussed in Section 2.6.1, are found as covalently connected dimers in which there is a disulfide bridge between a Cys residue located in a loop in the N-terminal extracellular domain of each monomer. This disulfide bridge apparently serves only to hold the monomers in close proximity, as the loop is so unstructured that it does not resolve in the x-ray structure. 

Calcium sensors are merely representative of a much wider class of ion sensors, albeit probably the best understood. Fluorescent probes have now been developed for a wide range of metal ions of biological interest, particularly sodium, potassium, magnesium, and zinc. 

Evanko, D. S. and Haydon, P. G. (2005). Elimination of environmental sensitivity in a cameleon FRET-based calcium sensor via replacement of the acceptor with Venus. Cell Calcium 37, 341-8. 

Fig. 10.3. Acceptor photobleaching analysis of interaction between barley MLO and calmodulin. Barley MLO is a plant-specific integral membrane protein that associates with the cytosolic calcium sensor protein Calmodulin...

Shortreed M., Kopelman R., Kuhn M., Hoyland B., Fluorescent Fiber-Optic Calcium Sensor for Physiological Measurements, Anal. Chem. 1996 68 1414-1418. 

Yang, J., McBride, S., Mak, D. O. etal. Identification of a family of calcium sensors as protein ligands of inositol trisphosphate receptor Ca(2+) release channels. Proc. Natl Acad. Sci. U.S.A. 99 7711-7716, 2002. 

Following these initial results, POWT was employed in the detection of protein conformational changes after a binding event. The protein used, calmodulin, is relatively small and functions as an intracellular calcium sensor in eukaryotic cells [26]. When calmodulin interacts with calcium, a large conformational change... 

The CASR functions as an extracellular calcium sensor for the parathyroid gland and the kidney. CASR serves to maintain a stable calcium concentration, without which many aspects of homeostasis are adversely affected. For example, the effect of CASR variants on seizure threshold in the brain is reviewed in Subheading... 

Calcium effects. The biochemical effects of Ca "" in the cytoplasm are mediated by special Ca -binding proteins calcium sensors"). These include the annexins, calmodulin, and troponin C in muscle (see p. 334). Calmodulin is a relatively small protein (17 kDa) that occurs in all animal cells. Binding of four Ca "" ions (light blue) converts it into a regulatory element. Via a dramatic conformational change (cf 2a and 2b), Ca -calmodulin enters into interaction with other proteins and modulates their properties. Using this mechanism, Ca "" ions regulate the activity of enzymes, ion pumps, and components of the cytoskeleton. 

Chin D, Means AR, Calmodulin A prototypical calcium sensor. Trends Cell Biol 10 322-328, 2000. 

Neurofibrillary tangles, aluminum associate with, 36 416-417 Neuromodulin, 46 449 Neuromuscular blocking agents, 36 7 Neuron-specific calcium sensor (NCS) proteins, 46 457... 

Monastyrskaya, K., Babiychuk, E.B., Hostettler, A., Rescher, U., and A. Draeger., 2006, Annexins as intracellular calcium sensors. Cell Calcium. 2006. 

Bourne, Y., Dannenberg, J., Pollmann, V., Marchot, P., and Pongs, O. (2001). Immunocytochemical localization and crystal structure of human frequenin (neuronal calcium sensor 1). J. Biol. Chem. 276 11949-11955. 

Flaherty, K.M., Zozulya, S., Stryer, L., and McKay, D.B. (1993). Three-dimensional structure of recoverin, a calcium sensor in vision. Cell 75 709—716. 

Otterbein LR, Kordowska J, Witte-Hoffmann C, Wang CL, Dominguez R. 2002. Crystal structures of S100A6 in the Ca(2+)-free and Ca(2+)-bound states the calcium sensor mechanism of S100 proteins revealed at atomic resolution. Structure 10(4) 557-567. 

SOCs, also known as ICRAC (calcium-release activated channels), have been observed in a wide range of cell types (Parekh and Penner, 1997). The defining property is that depletion of intracellular calcium stores results in increased calcium influx at the plasma membrane. The actual SOC that carries this calcium influx may vary between cells, and cloning studies have identified transient receptor potential channel (TRPC) (Parekh and Penner, 1997, Vandebrouck et al., 2002b) and CRACM1 (Peinelt et al., 2006) as candidate genes. Also, the exact mechanism by which SOCs are activated by store depletion has only been partly elucidated, with a role suggested for a calcium sensor on the endoplasmic reticulum (see Peinelt et al., 2006) and for IP3 (Kiselyov et al., 1998). 

Although bone is not considered a major calcium sensing organ in humans, the cells of bone tissue control over 99% of the human body s calcium content. The principal calcium sensors that regulate bone calcium uptake and release are in the parathyroid glands. Bone function is also modified by vitamin D and by calcium transport in the kidney and intestine. These indirect mechanisms of controlling bone calcium metabolism are beyond the scope of our considerations here. In spite of processing... 

The primary factor regulating PTH release is the level of calcium in the bloodstream.42 Parathyroid gland cells appear to act as calcium sensors that monitor circulating calcium levels. As circulating calcium levels fall below a certain point, PTH secretion is increased. Conversely, elevated plasma calcium titers inhibit PTH secretion. The ability of PTH to control plasma calcium levels and regulate bone mineral metabolism is discussed in more detail in Chapter 31... 

Caulfield MP, Jones S, Vallis Y, Buckley NJ, Kim GD, Milligan G, Brown DA (1994) Muscarinic M-current inhibition via G alpha q/11 and alpha-adrenoceptor inhibition of Ca2+ current via G alpha o in rat sympathetic neurones. J Physiol 477 Pt 3 415-22 Charvin N, L Eveque C, Walker D, Berton F, Raymond C, KataokaM, Shoji-Kasai Y, Takahashi M, De Waard M, Seagar MJ (1997) Direct interaction of the calcium sensor protein synaptotagmin I with a cytoplasmic domain of the alphal A subunit of the P/Q-type calcium channel. Embo J 16 4591-6... 

Fig. 4 Stages in synaptic vesicle exocytosis. Putative intermediate steps on the molecular pathway to synaptic vesicle fusion. Vesicle delivery and tethering to the presynaptic membrane most likely involves Rab-proteins and their effectors. So far, the nature of a speculative docking complex (dc) is unclear, but docking appears to be independent from SNARE proteins. In the primed state, SNAREs have assembled into a complex probably stabilized by complexin (Cpx). The fusion reaction is arrested until the intracellular calcium concentration increases. The putative calcium sensor for fast neurotransmitter release, synaptotagmin 1 (Syt), binds to intracellular calcium and in turn triggers fusion by associating with the presynaptic membrane and interacting with the SNARE complex, thereby displacing complexin (Tang et al. 2006).

The scope of ion-selective electrodes (ISEs) has been greatly enhanced by employing a poly(vinyl chloride) matrix to entangle sensor cocktail materials. Fbr ISFET devices an in situ photopolymerisation of monobutyl methacrylate provides a viable poly(butyl methacrylate) calcium sensor film with good gate adhesion properties. One or more enzymes can be chemically immobilized on modified nylon mesh. The resultant matrices are suitable for the amperometric assay of carbohydrates in blood and food products. 

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