calmoduliinMLCK

Calmodulin, a ubiquitous calcium-binding protein, plays a crucial role in cellular signaling. In muscle cells, it interacts with myosin light-chain kinase (MLCK), a key enzyme in the regulation of muscle contraction. This interaction, often referred to as calmodulin-MLCK, is a primary mechanism for controlling smooth muscle tone.

When intracellular calcium levels rise, calcium ions bind to calmodulin. This calcium-calmodulin complex then undergoes a conformational change, exposing a binding site that can interact with MLCK. The activated calcium-calmodulin complex binds to MLCK, leading to its activation. Activated MLCK then phosphorylates the regulatory light chains of myosin. This phosphorylation event is essential for initiating the cross-bridge cycling between actin and myosin filaments, which is the fundamental process of muscle contraction.

In smooth muscle, this calmodulin-MLCK pathway is particularly important because it is the main determinant of contraction force and duration. Relaxation occurs when calcium levels decrease, causing calcium to dissociate from calmodulin. This dissociation leads to the inactivation of MLCK and the dephosphorylation of myosin light chains, allowing the muscle to relax. Variations in the expression or activity of calmodulin or MLCK can have significant implications for physiological processes and can be implicated in various diseases associated with muscle dysfunction.