Aldosterone and nuclear signaling in kidney

Initiation of transcription is an early step in steroid hormone action. We investigated by means of atomic force microscopy (AFM) and fluorescence ima ging the role of nuclear pore complexes (NPCs) in mediating signal transduc tion of the mineralocorticoid hormone aldosterone from the extracellular sp ace into the cell nucleus. With AFM, we imaged single NPCs of isolated nucl ear envelopes under native conditions. We observed that individual NPCs con tract in response to a Ca2+ signal, which is known to occur in seconds afte r aldosterone exposure. In living kidney cells in culture (MDCK cells), ald osterone led within seconds to the contraction of the whole nucleus measure d by DNA-fluorescence imaging. Nuclear contraction was elicited at similar time scale and to similar extent by bradykinin, a peptide hormone known to mobilize Ca2+ from internal stores, and by ionomycin, a Ca2+ ionophore know n to directly increase intracellular Ca2+. Nuclear contraction is explained by the individual contraction of calcium-sensitive NPCs that occur in high density in the nuclear envelope. We present a model in which nuclear pore complexes play a key role as barrier molecules of high plasticity in the co ntrol of aldosterone-induced gene expression. (C) 1999 Elsevier Science Inc . All rights reserved.