Intracellular Calcium Homeostasis and Signaling

Abstract

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 released 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 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 tuned. Ca²⁺ is controlled by reversible complexation to specific proteins, which could be pure Ca²⁺ buffers, or which, in addition to buffering Ca²⁺, also decode its signal to pass it on to 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.