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J. Biol. Chem. 282 (6): 4210-4217

© 2007 by The American Society for Biochemistry and Molecular Biology, Inc.

Hormonal Regulation of Nuclear Permeability*{diamondsuit}

Elizabeth M. O'Brien, Dawidson A. Gomes, Sona Sehgal, , and Michael H. Nathanson1

Department of Medicine, Yale University School of Medicine, New Haven, Connecticut 06520-8019

Abstract: Transport into the nucleus is critical for regulation of gene transcription and other intranuclear events. Passage of molecules into the nucleus depends in part upon their size and the presence of appropriate targeting sequences. However, little is known about the effects of hormones or their second messengers on transport across the nuclear envelope. We used localized, two-photon activation of a photoactivatable green fluorescent protein to investigate whether hormones, via their second messengers, could alter nuclear permeability. Vasopressin and other hormones that increase cytosolic Ca2+ and activate protein kinase C increased permeability across the nuclear membrane of SKHep1 liver cells in a rapid unidirectional manner. An increase in cytosolic Ca2+ was both necessary and sufficient for this process. Furthermore, localized photorelease of caged Ca2+ near the nuclear envelope resulted in a local increase in nuclear permeability. Neither activation nor inhibition of protein kinase C affected nuclear permeability. These findings provide evidence that hormones linking to certain G protein-coupled receptors increase nuclear permeability via cytosolic Ca2+. Short term regulation of nuclear permeability may provide a novel mechanism by which such hormones permit transcription factors and other regulatory molecules to enter the nucleus, thereby regulating gene transcription in target cells.

Received for publication June 30, 2006. Revision received November 22, 2006.

* This work was supported by National Institutes of Health Grants DK45710, DK57751, DK07356, and DK34989. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

{diamondsuit} This article was selected as a Paper of the Week.

1 To whom correspondence should be addressed: Section of Digestive Diseases, Yale University School of Medicine, 1 Gilbert St., Rm. TAC S241D, New Haven, CT 06520-8019. Tel.: 203-785-7312; Fax: 203-785-4306; E-mail: michael.nathanson{at}

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