title: Multiple exportins influence thyroid hormone receptor localization.
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.
authors.affiliation: Department of Biology, College of William and Mary, Williamsburg, Virginia 23185, USA.
authors.forename: Kelly S
authors.initials: KS
authors.lastname: Subramanian
authors.affiliation: Department of Biology, College of William and Mary, Williamsburg, Virginia 23185, USA.
authors.forename: Rose C
authors.initials: RC
authors.lastname: Dziedzic
authors.affiliation: Department of Biology, College of William and Mary, Williamsburg, Virginia 23185, USA.
authors.forename: Hallie N
authors.initials: HN
authors.lastname: Nelson
authors.affiliation: Department of Biology, College of William and Mary, Williamsburg, Virginia 23185, USA.
authors.forename: Mary E
authors.initials: ME
authors.lastname: Stern
authors.affiliation: Department of Biology, College of William and Mary, Williamsburg, Virginia 23185, USA.
authors.forename: Vincent R
authors.initials: VR
authors.lastname: Roggero
authors.affiliation: Department of Biological Sciences, Hampton University, Hampton, Virginia 23668, USA.
authors.forename: Cornelius
authors.initials: C
authors.lastname: Bondzi
authors.affiliation: Department of Biology, College of William and Mary, Williamsburg, Virginia 23185, USA. Electronic address: laalli@wm.edu.
authors.forename: Lizabeth A
authors.initials: LA
authors.lastname: Allison
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000502:physiology*; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D028884:Karyopherins / Q000235:genetics / Q000378:metabolism*; D011988:Receptors, Thyroid Hormone / Q000378:metabolism*
chemical_list: D028884:Karyopherins; D011988:Receptors, Thyroid Hormone; C446511:XPO5 protein, human; C414440:Xpo4 protein, human
keywords: Exportin; Nuclear export; Thyroid hormone; Thyroid hormone receptor