Gacy, A. Marquis

Abstract The nuclear pore complex (NPC) is an excellent example of a bio-molecular motor, since it operates primarily via energy dependent processes, and performs some of the most vital functions required for the survival of a cell. In the presence of appropriate chemical stimuli, the NPC apparently opens or closes, like a gating mechanism, and permits the flow of material in to and out of the nucleus. An NPC, with typical dimensions of 100–200 nm, is a megadalton (MDa) heteromultimeric protein complex, which spans the nuclear envelope and is postulated to possess a transporter-containing central cylindrical body embedded between cytoplasmic and nucleoplasmic rings as shown in Fig.1. A cell has many, presumably identical, NPCs, each of which participates in the import and export of nuclear material from within the nucleus [1–2]. Exactly how this transport occurs through the NPC is an open question, and a very important one, with profound implications for nanoscale devices for fluidic transport, genetic engineering and targeted drug delivery.

Abstract —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 homeostasis. Although heart muscle is particularly sensitive to metabolic stress, the regulation of nuclear transport through nuclear pores in cardiomyocytes has not yet been characterized. With the use of laser confocal and atomic force microscopy, we observed nuclear transport in cardiomyocytes and the structure of individual nuclear pores under different cellular conditions. In response to the depletion of Ca 2+ stores or ATP/GTP pools, the cardiac nuclear pore complex adopted 2 distinct conformations that led to different patterns of nuclear import regulation. Depletion of Ca 2+ indiscriminately prevented the nuclear import of macromolecules through closure of the nuclear pore opening. Depletion of ATP/GTP only blocked facilitated transport through 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 nuclear pore complex, which was observed in response to changes in cellular conditions, identifies a gating mechanism for molecular translocation across the nuclear envelope of cardiac cells. The cardiac nuclear pore complex serves as a conduit that differentially regulates nuclear transport of macromolecules and provides a mechanism for the control of nucleocytoplasmic communication in cardiac cells, in particular under stress conditions associated with disturbances in cellular bioenergetics and Ca 2+ homeostasis.