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Dynamic shuttling and intranuclear mobility of nuclear hormone receptors.

Publication ,  Journal Article
Maruvada, P; Baumann, CT; Hager, GL; Yen, PM
Published in: J Biol Chem
April 4, 2003

We expressed green fluorescent protein (GFP) chimeras of estrogen, retinoic acid, and thyroid hormone receptors (ERs, RARs, and TRs, respectively) in HeLa cells to examine nucleocytoplasmic shuttling and intranuclear mobility of nuclear hormone receptors (NRs) by confocal microscopy. These receptors were predominantly in the nucleus and, interestingly, underwent intranuclear reorganization after ligand treatment. Nucleocytoplasmic shuttling was demonstrated by heterokaryon experiments and energy-dependent blockade of nuclear import and leptomycin-dependent blockade of nuclear export. Ligand addition decreased shuttling by GFP-ER, whereas heterodimerization with retinoid X receptor helped maintain TR and RAR within the nucleus. Intranuclear mobility of the GFP-NRs was studied by fluorescence recovery after photo-bleaching +/- cognate ligands. Both GFP-TR and GFP-RAR moved rapidly in the nucleus, and ligand binding did not significantly affect their mobility. In contrast, estrogen binding decreased the mobility of GFP-ER and also increased the fraction of GFP-ER that was unable to diffuse. These effects were even more pronounced with tamoxifen. Co-transfection of the co-activator, SRC-1, further slowed the mobility of liganded GFP-ER. Our findings suggest estradiol and tamoxifen exert differential effects on the intranuclear mobility of GFP-ER. They also show that ligand-binding and protein-protein interactions can affect the intracellular mobility of some NRs and thereby may contribute to their biological activity.

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Published In

J Biol Chem

DOI

ISSN

0021-9258

Publication Date

April 4, 2003

Volume

278

Issue

14

Start / End Page

12425 / 12432

Location

United States

Related Subject Headings

  • Receptors, Thyroid Hormone
  • Receptors, Retinoic Acid
  • Receptors, Estrogen
  • Receptors, Cytoplasmic and Nuclear
  • Plasmids
  • Luminescent Proteins
  • Ligands
  • Indicators and Reagents
  • Humans
  • Green Fluorescent Proteins
 

Citation

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Maruvada, P., Baumann, C. T., Hager, G. L., & Yen, P. M. (2003). Dynamic shuttling and intranuclear mobility of nuclear hormone receptors. J Biol Chem, 278(14), 12425–12432. https://doi.org/10.1074/jbc.M202752200
Maruvada, Padma, Christopher T. Baumann, Gordon L. Hager, and Paul M. Yen. “Dynamic shuttling and intranuclear mobility of nuclear hormone receptors.J Biol Chem 278, no. 14 (April 4, 2003): 12425–32. https://doi.org/10.1074/jbc.M202752200.
Maruvada P, Baumann CT, Hager GL, Yen PM. Dynamic shuttling and intranuclear mobility of nuclear hormone receptors. J Biol Chem. 2003 Apr 4;278(14):12425–32.
Maruvada, Padma, et al. “Dynamic shuttling and intranuclear mobility of nuclear hormone receptors.J Biol Chem, vol. 278, no. 14, Apr. 2003, pp. 12425–32. Pubmed, doi:10.1074/jbc.M202752200.
Maruvada P, Baumann CT, Hager GL, Yen PM. Dynamic shuttling and intranuclear mobility of nuclear hormone receptors. J Biol Chem. 2003 Apr 4;278(14):12425–12432.

Published In

J Biol Chem

DOI

ISSN

0021-9258

Publication Date

April 4, 2003

Volume

278

Issue

14

Start / End Page

12425 / 12432

Location

United States

Related Subject Headings

  • Receptors, Thyroid Hormone
  • Receptors, Retinoic Acid
  • Receptors, Estrogen
  • Receptors, Cytoplasmic and Nuclear
  • Plasmids
  • Luminescent Proteins
  • Ligands
  • Indicators and Reagents
  • Humans
  • Green Fluorescent Proteins