Calmodulin

by Jennifer McDowall

Calcium ions play a crucial role in the metabolism and physiology of eukaryotes.  Calcium exists as a gradient across the plasma membrane, with extracellular concentrations being about 10,000 times higher than intracellular ones.  External signals, such as hormones, light, stress or pathogenesis, can often lead to transient increases in calcium concentrations within the cell.  Cells have developed a multitude of ways to control and make use of this ion gradient to regulate many cellular processes, ranging from transcription control and cell survival to neurotransmitter release and muscle function.  Calcium participates in an intracellular signalling system by acting as a diffusible second messenger to the initial stimuli.  Increased calcium concentrations lead to calcium binding by regulatory proteins, which turn the calcium signal into a biological response.  There are many such regulatory proteins that bind calcium, which together form an intricate network of feedback loops to control the location, amount and effect of calcium influx.  Calmodulin is one such calcium-binding protein that is considered a major transducer of calcium signals.

Calmodulin, a calcium transducer

            Calmodulin (CaM) is a ubiquitous, calcium-binding protein that can bind to and regulate a multitude of different protein targets, thereby affecting many different cellular functions.  CaM mediates processes such as inflammation, metabolism, apoptosis, muscle contraction, intracellular movement, short-term and long-term memory, nerve growth and the immune response.  CaM is expressed in many cell types and can have different subcellular locations, including the cytoplasm, within organelles, or associated with the plasma or organelle membranes.  Many of the proteins that CaM binds are unable to bind calcium themselves, and as such use CaM as a calcium sensor and signal transducer.  CaM can also make use of the calcium stores in the endoplasmic reticulum, and the sarcoplasmic reticulum.  CaM undergoes a conformational change upon binding to calcium, which enables it to bind to specific proteins for a specific response.  CaM can bind up to four calcium ions, and can undergo post-translational modifications, such as phosphorylation, acetylation, methylation and proteolytic cleavage, each of which can potentially modulate its actions.