Multiple exportins influence thyroid hormone receptor localization

Mol Cell Endocrinol. 2015 Aug 15;411:86-96. doi: 10.1016/j.mce.2015.04.014. Epub 2015 Apr 21.

Abstract

The thyroid hormone receptor (TR) undergoes nucleocytoplasmic shuttling and regulates target genes involved in metabolism and development. Previously, we showed that TR follows a CRM1/calreticulin-mediated nuclear export pathway. However, two lines of evidence suggest TR also follows another pathway: export is only partially blocked by leptomycin B (LMB), a CRM1-specific inhibitor; and we identified nuclear export signals in TR that are LMB-resistant. To determine whether other exportins are involved in TR shuttling, we used RNA interference and fluorescence recovery after photobleaching shuttling assays in transfected cells. Knockdown of exportins 4, 5, and 7 altered TR shuttling dynamics, and when exportins 5 and 7 were overexpressed, TR distribution shifted toward the cytosol. To further assess the effects of exportin overexpression, we examined transactivation of a TR-responsive reporter gene. Our data indicate that multiple exportins influence TR localization, highlighting a fine balance of nuclear import, retention, and export that modulates TR function.

Keywords: Exportin; Nuclear export; Thyroid hormone; Thyroid hormone receptor.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Active Transport, Cell Nucleus / physiology*
  • Cell Nucleus / metabolism
  • Cytoplasm / metabolism
  • HeLa Cells
  • Humans
  • Karyopherins / genetics
  • Karyopherins / metabolism*
  • Receptors, Thyroid Hormone / metabolism*

Substances

  • Karyopherins
  • Receptors, Thyroid Hormone
  • XPO5 protein, human
  • Xpo4 protein, human