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• W1977274674 startingPage "3775" @default.
• W1977274674 abstract "The mechanism by which glucocorticoids induce various cellular responses in different tissues is only partially understood. Here we demonstrate that glucocorticoids stabilize the actin cytoskeleton of several cell types, as revealed by increased resistance of actin filaments to the disrupting effect of cytochalasin and by visible thickening of actin filament bundles. These effects require several hours to develop, require protein synthesis, and are accompanied by increased expression of the actin-binding protein caldesmon. These data may help to explain why glucocorticoids inhibit corticotropin release from pituitary cells, if interpreted in terms of the current idea that an actin filament barrier modulates exocytotic secretion in various cell types. In support of this idea, we find that in model corticotrophs (AtT-20 cells), glucocorticoids stabilize actin filaments and inhibit corticotropin release with similar potencies. Furthermore, we show here that glucocorticoid inhibition is overcome by exposing AtT-20 cells to concentrations of cytochalasin B or D that disrupt their stabilized actin filaments. On the other hand, our freeze-etch electron microscopy of AtT-20 cells has shown that actin filaments do not, in fact, create a dense submembranous barrier that might prevent corticotropin secretory droplets from discharging; instead, they form open networks near the membrane that appear to hold secretory droplets in their interstices. We propose that the delicate physical crosslinks maintaining this actin-mediated membrane docking of secretory droplets may need to disconnect in order to permit corticotropin discharge and that these crosslinks may be stabilized along with the actin filaments in dexamethasone-treated cells." @default.
• W1977274674 created "2016-06-24" @default.
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• W1977274674 date "1992-05-01" @default.
• W1977274674 modified "2023-10-03" @default.
• W1977274674 title "Glucocorticoid stabilization of actin filaments: a possible mechanism for inhibition of corticotropin release." @default.
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• W1977274674 doi "https://doi.org/10.1073/pnas.89.9.3775" @default.
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