Structural plasticity of the cardiac nuclear pore complex in response to regulators of nuclear import

Communication between the cytoplasm and nucleoplasm of cardiac cells occurs by molecular transport through nuclear pores. In lower eukaryotes, nuclear transport requires the maintenance of cellular energetics and ion homeosta sis. Although heart muscle is particularly sensitive to metabolic stress, t he regulation of nuclear transport through nuclear pores in cardiomyocytes has not yet been characterized. With the use of laser confocal and atomic f orce microscopy, we observed nuclear transport in cardiomyocytes and the st ructure of individual nuclear pores under different cellular conditions. In response to the depletion of Ca2+ stores or ATP/GTP pools, the cardiac nuc lear pore complex adopted 2 distinct conformations that led to different pa tterns of nuclear import regulation. Depletion of Ca2+ indiscriminately pre vented the nuclear import of macromolecules through closure of the nuclear pore opening. Depletion of ATP/GTP only blocked facilitated transport throu gh a simultaneous closure of the pore and relaxation of the entire complex, which allowed other molecules to pass into the nucleus through peripheral routes. The current study of the structural plasticity of the cardiac nucle ar pore complex, which was observed in response to changes in cellular cond itions, identifies a gating mechanism for molecular translocation across th e nuclear envelope of cardiac cells. The cardiac nuclear pore complex serve s as a conduit that differentially regulates nuclear transport of macromole cules and provides a mechanism for the control of nucleocytoplasmic communi cation in cardiac cells, in particular under stress conditions associated w ith disturbances in cellular bioenergetics and Ca2+ homeostasis.