Let go or retain: role of calmodulin in orchestrating nuclear protein transport in eukaryotes

Protein transport is a tightly regulated and complex cellular process fundamental to growth and development. A critical aspect of this process is the accurate and timely translocation of transcription factors and other components of the transcriptional machinery into the nucleus, which is indispensable for the regulation of gene expression. Calmodulin (CaM), a conserved calcium-sensing protein, binds 4 calcium ions and, upon activation, triggers a cascade of signaling events that fine-tune transcriptional outcomes. Notably, CaM exerts a dual regulatory role-facilitating or inhibiting the nuclear import of proteins depending on the cellular context. This review provides a detailed account of the structure and function of CaM, elucidates the molecular basis of its interactions with nuclear transport components, and presents case studies that substantiate its role as a modulator of nuclear protein trafficking across diverse organisms, including recent findings in plants. In addition, we have summarized the potential future applications and implications of CaM-mediated nuclear transport. This finding paves the way for further exploration of how calcium-signaling and CaM-mediated protein transport shape plant development and stress responses. Beyond elucidating the complex regulation of protein localization in plant cells, this insight may also offer new strategies for enhancing plant growth, development, and resilience under stress conditions.