Directed Inhibition of Nuclear Import in Cellular Hypertrophy

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

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Each nuclear pore is responsible for both nuclear import and export with a finite capacity for bidirectional transport across the nuclear envelope. It remains poorly understood how the nuclear transport pathway responds to increased demands for nucleocytoplasmic communication. A case in point is cellular hypertrophy in which increased amounts of genetic material need to be transported from the nucleus to the cytosol. Here, we report an adaptive down-regulation of nuclear import supporting such an increased demand for nuclear export. The induction of cardiac cell hypertrophy by phenylephrine or angiotensin II inhibited the nuclear translocation of H1 histones. The removal of hypertrophic stimuli reversed the hypertrophic phenotype and restored nuclear import. Moreover, the inhibition of nuclear export by leptomycin B rescued import. Hypertrophic reprogramming increased the intracellular GTP/GDP ratio and promoted the nuclear redistribution of the GTP-binding transport factor Ran, favoring export over import. Further, in hypertrophy, the reduced creatine kinase and adenylate kinase activities limited energy delivery to the nuclear pore. The reduction of activities was associated with the closure of the cytoplasmic phase of the nuclear pore preventing import at the translocation step. Thus, to overcome the limited capacity for nucleocytoplasmic transport, cells requiring increased nuclear export regulate the nuclear transport pathway by undergoing a metabolic and structural restriction of nuclear import.

Original languageEnglish (US)
Pages (from-to)20566-20571
Number of pages6
JournalJournal of Biological Chemistry
Volume276
Issue number23
DOIs
StatePublished - Jun 8 2001

Fingerprint

Cell Nucleus Active Transport
Guanosine Triphosphate
Hypertrophy
Adenylate Kinase
Phenylephrine
Creatine Kinase
Angiotensin II
Histones
Cells
Nuclear Pore
Communication
Nuclear Envelope
Cardiomegaly
Cytosol
leptomycin B
Down-Regulation
Phenotype

ASJC Scopus subject areas

  • Biochemistry

Cite this

Directed Inhibition of Nuclear Import in Cellular Hypertrophy. / Terzic, Carmen M; Gacy, A. Marquis; Bortolon, Ryan; Dzeja, Petras P; Puceat, Michel; Jaconi, Marisa; Prendergast, Franklyn G.; Terzic, Andre.

In: Journal of Biological Chemistry, Vol. 276, No. 23, 08.06.2001, p. 20566-20571.

Research output: Contribution to journalArticle

Terzic, CM, Gacy, AM, Bortolon, R, Dzeja, PP, Puceat, M, Jaconi, M, Prendergast, FG & Terzic, A 2001, 'Directed Inhibition of Nuclear Import in Cellular Hypertrophy', Journal of Biological Chemistry, vol. 276, no. 23, pp. 20566-20571. https://doi.org/10.1074/jbc.M101950200
Terzic, Carmen M ; Gacy, A. Marquis ; Bortolon, Ryan ; Dzeja, Petras P ; Puceat, Michel ; Jaconi, Marisa ; Prendergast, Franklyn G. ; Terzic, Andre. / Directed Inhibition of Nuclear Import in Cellular Hypertrophy. In: Journal of Biological Chemistry. 2001 ; Vol. 276, No. 23. pp. 20566-20571.
@article{d323119da1654499817594e69b457ecf,
title = "Directed Inhibition of Nuclear Import in Cellular Hypertrophy",
abstract = "Each nuclear pore is responsible for both nuclear import and export with a finite capacity for bidirectional transport across the nuclear envelope. It remains poorly understood how the nuclear transport pathway responds to increased demands for nucleocytoplasmic communication. A case in point is cellular hypertrophy in which increased amounts of genetic material need to be transported from the nucleus to the cytosol. Here, we report an adaptive down-regulation of nuclear import supporting such an increased demand for nuclear export. The induction of cardiac cell hypertrophy by phenylephrine or angiotensin II inhibited the nuclear translocation of H1 histones. The removal of hypertrophic stimuli reversed the hypertrophic phenotype and restored nuclear import. Moreover, the inhibition of nuclear export by leptomycin B rescued import. Hypertrophic reprogramming increased the intracellular GTP/GDP ratio and promoted the nuclear redistribution of the GTP-binding transport factor Ran, favoring export over import. Further, in hypertrophy, the reduced creatine kinase and adenylate kinase activities limited energy delivery to the nuclear pore. The reduction of activities was associated with the closure of the cytoplasmic phase of the nuclear pore preventing import at the translocation step. Thus, to overcome the limited capacity for nucleocytoplasmic transport, cells requiring increased nuclear export regulate the nuclear transport pathway by undergoing a metabolic and structural restriction of nuclear import.",
author = "Terzic, {Carmen M} and Gacy, {A. Marquis} and Ryan Bortolon and Dzeja, {Petras P} and Michel Puceat and Marisa Jaconi and Prendergast, {Franklyn G.} and Andre Terzic",
year = "2001",
month = "6",
day = "8",
doi = "10.1074/jbc.M101950200",
language = "English (US)",
volume = "276",
pages = "20566--20571",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "23",

}

TY - JOUR

T1 - Directed Inhibition of Nuclear Import in Cellular Hypertrophy

AU - Terzic, Carmen M

AU - Gacy, A. Marquis

AU - Bortolon, Ryan

AU - Dzeja, Petras P

AU - Puceat, Michel

AU - Jaconi, Marisa

AU - Prendergast, Franklyn G.

AU - Terzic, Andre

PY - 2001/6/8

Y1 - 2001/6/8

N2 - Each nuclear pore is responsible for both nuclear import and export with a finite capacity for bidirectional transport across the nuclear envelope. It remains poorly understood how the nuclear transport pathway responds to increased demands for nucleocytoplasmic communication. A case in point is cellular hypertrophy in which increased amounts of genetic material need to be transported from the nucleus to the cytosol. Here, we report an adaptive down-regulation of nuclear import supporting such an increased demand for nuclear export. The induction of cardiac cell hypertrophy by phenylephrine or angiotensin II inhibited the nuclear translocation of H1 histones. The removal of hypertrophic stimuli reversed the hypertrophic phenotype and restored nuclear import. Moreover, the inhibition of nuclear export by leptomycin B rescued import. Hypertrophic reprogramming increased the intracellular GTP/GDP ratio and promoted the nuclear redistribution of the GTP-binding transport factor Ran, favoring export over import. Further, in hypertrophy, the reduced creatine kinase and adenylate kinase activities limited energy delivery to the nuclear pore. The reduction of activities was associated with the closure of the cytoplasmic phase of the nuclear pore preventing import at the translocation step. Thus, to overcome the limited capacity for nucleocytoplasmic transport, cells requiring increased nuclear export regulate the nuclear transport pathway by undergoing a metabolic and structural restriction of nuclear import.

AB - Each nuclear pore is responsible for both nuclear import and export with a finite capacity for bidirectional transport across the nuclear envelope. It remains poorly understood how the nuclear transport pathway responds to increased demands for nucleocytoplasmic communication. A case in point is cellular hypertrophy in which increased amounts of genetic material need to be transported from the nucleus to the cytosol. Here, we report an adaptive down-regulation of nuclear import supporting such an increased demand for nuclear export. The induction of cardiac cell hypertrophy by phenylephrine or angiotensin II inhibited the nuclear translocation of H1 histones. The removal of hypertrophic stimuli reversed the hypertrophic phenotype and restored nuclear import. Moreover, the inhibition of nuclear export by leptomycin B rescued import. Hypertrophic reprogramming increased the intracellular GTP/GDP ratio and promoted the nuclear redistribution of the GTP-binding transport factor Ran, favoring export over import. Further, in hypertrophy, the reduced creatine kinase and adenylate kinase activities limited energy delivery to the nuclear pore. The reduction of activities was associated with the closure of the cytoplasmic phase of the nuclear pore preventing import at the translocation step. Thus, to overcome the limited capacity for nucleocytoplasmic transport, cells requiring increased nuclear export regulate the nuclear transport pathway by undergoing a metabolic and structural restriction of nuclear import.

UR - http://www.scopus.com/inward/record.url?scp=0035827618&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035827618&partnerID=8YFLogxK

U2 - 10.1074/jbc.M101950200

DO - 10.1074/jbc.M101950200

M3 - Article

C2 - 11283025

AN - SCOPUS:0035827618

VL - 276

SP - 20566

EP - 20571

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 23

ER -