Cytoplasm-to-nucleus Shuttling of Thyroid Hormone Receptor-beta1 (Trbeta1) is Directed from a Plasma Membrane Integrin Receptor by Thyroid Hormone

Introduction: In CV-1 cells, shuttling from cytoplasm to nucleus of the nuclear thyroid hormone receptor-beta1 (TRbeta1, TR) is shown in this report to be regulated by extracellular thyroid hormone at a hormone receptor on cell surface integrin alphav3.

Methods: The receptor was introduced into cells as a GFP-TR1 chimera and intracellular movement of the receptor was monitored by confocal microscopy of cells treated with L-thyroxine (T(4)).

Results And Discussion: TR-GFP translocation in the presence of T(4) requires activation of extracellular-regulated protein kinases 1/2 (ERK1/2). Inhibition of T(4)-binding to alphavbeta3 with anti-alphavbeta3 or Arg-Gly-Asp (RGD) peptide blocks T(4)-stimulated GFP-TR nuclear translocation, as do the hormone-binding inhibitor tetraiodothyroacetic acid (tetrac) and the ERK1/2 inhibitor, PD98059. TR1 is an ERK1/2 substrate.

Conclusions: Via a nongenomic mechanism initiated at plasma membrane integrin v3, T(4)-activated ERK1/2 and TR1 move transiently in an immunoprecipitable complex to the nuclei of T(4)-treated cells.