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First published online February 23, 2005
doi: 10.1242/10.1242/jcs.01705

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Another dimension to calcium signaling: a look at extracellular calcium

VA Boston Healthcare System and Brigham & Women's Hospital, Department of Surgery, Harvard Medical School, 1400 VFW Parkway, West Roxbury, MA 02132, USA

e-mail: ahofer{at}rics.bwh.harvard.edu

Cell biologists know the calcium ion best as a vital intracellular second messenger that governs countless cellular functions. However, the recent identification of cell-surface detectors for extracellular Ca²⁺ has prompted consideration of whether Ca²⁺ also functions as a signaling molecule in the extracellular milieu. The cast of Ca²⁺ sensors includes the well-characterized extracellular-Ca²⁺-sensing receptor, a G-protein-coupled receptor originally isolated from the parathyroid gland. In addition, other receptors, channels and membrane proteins, such as gap junction hemichannels, metabotropic glutamate receptors, HERG K⁺ channels and the receptor Notch, are all sensitive to external [Ca²⁺] fluctuations. A recently cloned Ca²⁺ sensor (CAS) in Arabidopsis extends this concept to the plant kingdom. Emerging evidence indicates that [Ca²⁺] in the local microenvironment outside the cell undergoes alterations potentially sufficient to exert biological actions through these sensor proteins. The extracellular space might therefore constitute a much more dynamic Ca²⁺ signaling compartment than previously appreciated.

Key words: Parathyroid extracellular-Ca²⁺-sensing receptor (CaR), Hemichannels, ASIC, Endocytosis, Notch, Plant Ca²⁺ sensor (CAS)

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