CaMdependent

CaM-dependent, or calmodulin-dependent, refers to cellular processes and enzymes regulated by calmodulin in its calcium-bound form. Calmodulin is a small, ubiquitous calcium-binding messenger protein that detects changes in intracellular Ca2+ and translates them into regulatory signals. When Ca2+ levels rise, Ca2+ binds to CaM, inducing a conformational change that allows Ca2+/CaM to interact with a diverse set of target proteins and modify their activity.

Prominent examples include Ca2+/CaM-dependent protein kinases (CaMKs), especially CaMKII and CaMKIV, which phosphorylate substrates involved in synaptic transmission, learning, and memory. The CaM-dependent phosphatase calcineurin (protein phosphatase 2B) dephosphorylates NFAT transcription factors and other substrates, influencing gene expression and immune responses. Myosin light chain kinase (MLCK) is activated by Ca2+/CaM and drives smooth muscle contraction. Some calcium-stimulated enzymes, including certain adenylyl cyclases (AC1, AC8) and phosphodiesterases (PDE1 family), are regulated directly by Ca2+/CaM to modulate cyclic nucleotide signaling. Nitric oxide synthases (nNOS and eNOS) also require Ca2+/CaM for activity, linking calcium signals to NO production.

In physiology, CaM-dependent pathways govern neuronal signaling, muscle contraction, vascular tone, and immune responses, and they contribute to synaptic plasticity and gene expression. Dysregulation of CaM-dependent signaling has been implicated in cardiac arrhythmias, neurodegenerative diseases, and other disorders. Research on CaM-dependent mechanisms continues to clarify how calcium signals are integrated to produce precise cellular outcomes.