Cell 131, December 14, 2007: 1049

Calcium ions (Ca2+) impact nearly every aspect of cellular life. This review examines the principles of Ca2+ signaling, from changes in protein conformations driven by Ca2+ to the mechanisms that control Ca2+ levels in the cytoplasm and organelles. Also discussed is the highly localized nature of Ca2+-mediated signal transduction and its specific roles in excitability, exocytosis, motility, apoptosis, and transcription.
In the furnaces of the stars the elements evolved from hydrogen. When oxygen and neon captured successive
α particles, the element calcium was born. Roughly 10 billion years later, cell membranes began to parse the
world by charge, temporarily and locally defying relentless entropy. To adapt to changing environments, cells
must signal, and signaling requires messengers whose concentration varies with time. Filling this role, calcium
ions (Ca2+) and phosphate ions have come to rule cell signaling. Here, I describe our current understanding of
Ca2+ -mediated signaling (complementing several excellent reviews [Berridge, 2005; Burgoyne, 2007; Carafoli,
2004; Petersen, 2005; Rizzuto and Pozzan, 2006]) and place particular emphasis on emerging themes related
to Ca 2+ binding proteins, Ca 2+ entry across the plasma membrane, and the localized nature of Ca2+ signals.