Calcium Signaling

This volume contains a unique selection of chapters covering a wealth of contemporary topics in this ubiquitous and diverse system of cell signaling. It offers much more than the accessibility and authority of a primary text book, exploring topics ranging

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Calcium Binding Proteins Matilde Yáñez, José Gil-Longo, and Manuel Campos-Toimil

Abstract The role of Ca2+ as a key and pivotal second messenger in cells depends largely on a wide number of heterogeneous so-called calcium binding proteins (CBP), which have the ability to bind this ion in specific domains. CBP contribute to the control of Ca2+ concentration in the cytosol and participate in numerous cellular functions by acting as Ca2+ transporters across cell membranes or as Ca2+modulated sensors, i.e., decoding Ca2+ signals. In this chapter we review the main Ca2+-modulated CBP, starting with those intracellular CBP that contain the structural EF-hand domain: parvalbumin, calmodulin, S100 proteins and calcineurin. Then, we address intracellular CBP lacking the EF-hand domain: CBP within intracellular Ca2+ stores (paying special attention to calreticulin and calsequestrin), annexins and proteins that contain a C2 domain, such as protein kinase C (PKC) or sinaptotagmin. Finally, extracellular CBP have been classified in six groups, according to their Ca2+ binding structures: (i) EF-hand domains; (ii) EGF-like domains; (iii) g-carboxyl glutamic acid (GLA)-rich domains; (iv) cadherin domains; (v) Ca2+dependent (C)-type lectin-like domains; (vi) Ca2+-binding pockets of family C G-protein-coupled receptors. For all proteins, we briefly review their structure, location and function and additionally their potential as pharmacological targets in several human diseases. Keywords Ca2+ binding proteins • EF-hand domain • Ca2+ sensors

M. Yáñez • J. Gil-Longo • M. Campos-Toimil (*) Departamento de Farmacoloxía. Facultade de Farmacia, Universidade de Santiago de Compostela, Campus Vida, E-15782, Santiago de Compostela, Spain e-mail: [email protected] M.S. Islam (ed.), Calcium Signaling, Advances in Experimental Medicine and Biology 740, DOI 10.1007/978-94-007-2888-2_19, © Springer Science+Business Media Dordrecht 2012

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Introduction Ca2+ binding proteins (CBP) are a heterogeneous and wide group of proteins that participate in numerous cellular functions (e.g. Ca2+ homeostasis and Ca2+ signaling pathways), thus regulating animal and plant cell function. Although they have different structures and properties, most CBP selectively and reversibly bind Ca2+ in specific domains, the kinetics of this interaction being very fast. It has been suggested by Carafoli et al. [1] that CBP could be subdivided into two categories: membrane-intrinsic CBP that modulate Ca2+ concentration in the environment by transporting it across cell membranes and Ca2+-modulated proteins. This last group includes proteins that not only contribute to the control of Ca2+ concentration, but also to decode Ca2+ signals, acting as Ca2+ sensors. According to this classification, in this chapter we have briefly reviewed the main Ca2+-modulated CBP, focussing on their respective structures, location and functions and, in some cases, on their potential role as therapeutic targets in several pathologies [1, 2]. Ca2+ transporters and chann