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(Circulation Research. 1999;84:1292-1301.)
© 1999 American Heart Association, Inc.

Original Contributions

Structural Plasticity of the Cardiac Nuclear Pore Complex in Response to Regulators of Nuclear Import

Carmen Perez-Terzic, A. Marquis Gacy, Ryan Bortolon, Petras P. Dzeja, Michel Puceat, Marisa Jaconi, Franklyn G. Prendergast, Andre Terzic

From the Division of Cardiovascular Diseases and Department of Internal Medicine (C.P.-T., P.P.D., M.P., M.J., A.T.), the Department of Physical Medicine and Rehabilitation (C.P.-T.), and the Department of Pharmacology (A.M.G., R.B., F.G.P., A.T.), Mayo Clinic, Rochester, Minn. The current affiliation for Michel Puceat is Centre de Recherches de Biochimie Macromoleculaires, Montpellier, France. The current affiliation for Marisa Jaconi is Biology of Aging Laboratory, Geriatric Hospital, Geneva, Switzerland.

Correspondence to A. Terzic, Guggenheim-7, Mayo Clinic, Rochester, MN 55905. E-mail terzic.andre{at}mayo.edu

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 Ca²⁺ 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 Ca²⁺ 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 Ca²⁺ homeostasis.

Key Words: nucleus • transport • Ca²⁺ • ATP • GTP • stress, cellular • microscopy

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