STIM-TRP Pathways
Receptor-evoked Ca2+ influx is a central component of the Ca2+ signal. A ubiquitous form of Ca2+ influx is activated by depletion of endoplasmic Ca2+ stores, the SOC channels. The two established Ca2+ influx channels that are activated by depletion of the
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STIM-TRP Pathways The STIM1/Orai/TRPC Channels Multiple Ca Complexes
2+
Influx
Jeong Hee Hong, Min Seuk Kim, Kyu Pil Lee, Joseph P. Yuan, and Shmuel Muallem
5.1
Introduction
Changes in cytoplasmic Ca2+ ([Ca2+]i) are fundamental form of cellular signal transduction, with Ca2+ signaling regulating virtually all cellular functions on time scales from msec to days (Berridge et al. 2003). At the same time, persistent elevation in [Ca2+]i is highly toxic and is the underlying cause of cell toxicity observed in multiple diseases associated with many forms of cell stress, such as ER stress, autoimmune attacks, and inflammation (Nilius et al. 2008; Petersen et al. 2006; Petersen and Tepikin 2008). The cells thus use an elaborate homeostatic system with numerous regulatory sites to tightly control [Ca2+]i at all times. The fundamental [Ca2+]i homeostatic system includes (1) the plasma membrane (PMCA) and ER/SR (SERCA) Ca2+ pumps that remove Ca2+ from the cytosol and (2) the ER resident IP3 and ryanodine receptors (RyRs) as well as multiple Ca2+ influx channels at the plasma membrane that add Ca2+ to the cytosol (Kiselyov et al. 2006; Mikoshiba 2007; Hamilton and Serysheva 2009). Superimposed on this fundamental system are several intracellular Ca2+ handling organelles that help to control [Ca2+]i, on the one hand, with their function regulated by Ca2+, on the other hand. The most prominent organelle is the mitochondria (Rizzuto and Pozzan 2006), with further contribution by the acidic Ca2+ storage system that include the lysosomal and endosomal systems (Brini and Carafoli 2009), the
J.H. Hong • M.S. Kim • K.P. Lee • S. Muallem (*) Epithelial Signaling and Transport Section, Molecular Physiology and Therapeutics Branch, NIDCR, NIH, Bethesda, MD, USA e-mail: [email protected] J.P. Yuan Department of Integrative Physiology, University of North Texas Health Sciences Center, Fort Worth, TX, USA K. Groschner et al. (eds.), Store-operated Ca2+ entry (SOCE) pathways, DOI 10.1007/978-3-7091-0962-5_5, # Springer-Verlag/Wien 2012
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acidocalciosomal system (Van Baelen et al. 2004) and the secretory granule system in secretory cells (Wuytack et al. 2002). The basic receptor-evoked Ca2+ signal is initiated by generation of the second messenger IP3 due to activation of phospholipases (PLCb and PLCg) to trigger Ca2+ release from the ER. This can be preceded or followed by Ca2+ release from associated stores that express RyRs and by Ca2+ release from physically and functionally separate stores in intracellular organelles (Berridge 2006; Petersen and Tepikin 2008). It is clear that Ca2+ release from the ER leads to activation of Ca2+ influx channels at the plasma membrane (Parekh and Putney 2005) , but it is not known whether Ca2+ release exclusively from ER-independent stores can also trigger activation of Ca2+ influx channels, at least in cellular microdomains. At weak stimulus intensity, Ca2+ release is then terminated by the combination of reduced production of IP3 to inhibit the Ca2+ release and by p
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