Aldosterone and nuclear signaling in kidney

Abstract

Initiation of transcription is an early step in steroid hormone action. We investigated by means of atomic force microscopy (AFM) and fluorescence imaging the role of nuclear pore complexes (NPCs) in mediating signal transduction of the mineralocorticoid hormone aldosterone from the extracellular space into the cell nucleus. With AFM, we imaged single NPCs of isolated nuclear envelopes under native conditions. We observed that individual NPCs contract in response to a Ca 2+ signal, which is known to occur in seconds after aldosterone exposure. In living kidney cells in culture (MDCK cells), aldosterone led within seconds to the contraction of the whole nucleus measured by DNA-fluorescence imaging. Nuclear contraction was elicited at similar time scale and to similar extent by bradykinin, a peptide hormone known to mobilize Ca 2+ from internal stores, and by ionomycin, a Ca 2+ ionophore known to directly increase intracellular Ca 2+. 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 control of aldosterone-induced gene expression.