A novel model for nuclear receptor action

ERLEJMAN A.G.; LAGADARI M.; QUINTÁ H.R.; PIWIEN PILIPUK G.; GALIGNIANA M.D.

RECENT ADVANCES IN MOLECULAR AND CELLULAR BIOLOGY

Global Research

Lugar: Londres; Año: 2010; p. 1 - 11

Inasmuch as the biological function of signaling cascade factors is determined by their cellular localization and subsequent interactions with other factors in a given subcellular compartment, it is critical to understand how these proteins move to and from the sites where they exert biological effects. Even though it is well known that transport of soluble proteins enclosed into vesicles follows the molecular mechanism associated to the vesicle transport, the movement of soluble proteins not associated to vesicles is a pending assignment of the Cell Biology field. In this regard, steroid receptors are a superb model to analyze this phenomenon. In the absence of hormone, some receptors such as the glucocorticoid receptor (GR) and the mineralocorticoid receptor (MR) are primarily located in the cytoplasm. Upon steroid-binding, they rapidly accumulate in the nucleus. Regardless of their primary location, these receptors undergo a constant and dynamic nucleocytoplasmic shuttling. Such movement has always been assumed to occur in a stochastic manner by simple diffusion. Although heuristic, this oversimplified model has never been demonstrated. Morevover, it has always been assumed that the first step that permits the nuclear import of steroid receptors is the dissociation of the hsp90-based heterocomplex, a process normally referred to as transformation. Nonetheless, experimental evidence supports an opposite model where the chaperone machinery is required for the retrotransport of the receptor throughout the cytoplasm and also facilitates the passage through the nuclear pore, so that it becomes apparent that transformation is actually a nuclear event.