Evolution and significance of CaM KMT- Calmodulin interaction- A journey of more than 40 years

The calmodulin (CaM) family serves as the primary calcium sensor. Upon receiving calcium signals, CaM binds calcium ions and regulates the activity of numerous effector proteins. In plants, several CaM-binding proteins have been identified and their roles are gradually becoming clear. CaM functions through interactions with short peptide sequences in target proteins, inducing conformational changes that modulate their activity in response to fluctuations in intracellular calcium. CaM-binding proteins, including transcription factors, ion channels and metabolic enzymes, enable plants to efficiently respond to environmental stresses and pathogen attacks. Studies employing genetic, molecular and biochemical approaches have provided valuable insights into CaM’s role in regulating diverse targets to enhance stress resistance. Despite this progress, limited research has addressed CaM -lysine N-methyltransferase (CaM KMT), a crucial regulator of CaM. CaM KMT specifically trimethylates one specific lysine residue of CaM proteins, thereby influencing their function. This review summarizes research on CaM and its regulator CaM KMT, with a focus on Ca2+/CaM-mediated regulation of plant responses to abiotic and biotic stresses, the role of lysine methylation in CaM function, the discovery and implications of CaM Lys-116 methylation and CaM KMT-mediated regulation across plants and animals. In conclusion, while substantial progress has been achieved in understanding CaM signalling, the role of CaM KMT remains underexplored. Future studies integrating structural, functional genomics and evolutionary approaches will be critical to clarify CaM KMT-mediated regulation, with implications for engineering stress-resilient crops.