Rapid non-classical effects of steroids on the membrane receptor dynamics and downstream signaling in neurons

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Contribution to Special Issue on Fast effects of steroids.

Although rapid effects of steroid hormones on membrane receptors and intracellular signaling molecules have been extensively studied in neurons, we are only beginning to understand the molecular mechanisms behind these non-classical steroid actions. Single molecule tracking (SMT) studies on live cells demonstrated that surface trafficking of membrane receptors determines their ligand binding properties and downstream signaling events. Recent findings suggest that one of the underlying mechanisms of non-classical steroid actions is the alteration of receptor movements on the membrane surface. In order to highlight this novel aspect of steroid effects, we first address the types of receptor movements in the plasma membrane and the role of cortical actin dynamics in receptor movement. We then discuss how single molecules and the surface movements of receptors can be detected in live cells. Next, we review the fundamental processes, which determine the effect of steroids on the plasma membrane: steroid movement through the lipid bilayer and the role of steroid membrane receptors. Using glutamate and neurotrophin receptors (NTRs) as examples, we demonstrate the features of receptor dynamics in the membrane. In addition, we survey the available data of rapid steroid actions on membrane receptor trafficking: we discuss how glucocorticoids act on the surface diffusion of glutamate receptor molecules and how estradiol acts on NTRs and gamma-aminobutyric acid type A receptors (GABAARs) and their related signaling events as well as on cortical actin. Finally, we address the physiological relevance of rapid steroid action on membrane receptors dynamics.

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