Intracellular Calcium Homeostasis and Signaling

Ca2+ is a universal carrier of biological information: it controls cell life from its origin at fertilization to its end in the process of programmed cell death. Ca2+ is a conventional diffusible second messenger generated inside cells by the interaction of first messengers with plasma membrane receptors. However, it can also penetrate directly into cells to deliver information without the intermediation of first or second messengers. Even more distinctively, Ca2+ can also act as a first messenger, by interacting with a plasma membrane receptor to set in motion intracellular signaling pathways that involve Ca2+ itself. Perhaps the most distinctive property of the Ca2+ signal is its ambivalence: while essential to the correct functioning of cells, Ca2+ becomes an agent that mediates cell distress, or even (toxic) cell death, if its concentration and movements inside cells are not carefully controlled. Ca2+ is controlled by reversible complexation to specific proteins, which could be pure Ca2+ buffers, or which, in addition to buffering to Ca2+, also decode its signal to pass it targets. The most important actors in the buffering of cell Ca2+ are proteins that transport it across the plasma membrane and the membrane of the organelles: some have high Ca2+ affinity and low transport capacity (e.g., Ca2+ pumps), others have opposite properties (e.g., the Ca2+ uptake system of mitochondria). Between the initial event of fertilization, and the terminal event of programmed cell death, the Ca2+ signal regulates the most important activities of the cell, from the expression of genes, to heart and muscle contraction and other motility processes, to diverse metabolic pathways involved in the generation of cell fuels.