Glucocorticoid stabilization of actin filaments: A possible mechanism for inhibition of corticotropin release

Flora Castellino, John Heuser, Sabrina Marchetti, Bernardino Bruno, Alberto Luini

Research output: Contribution to journalArticle

81 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)3775-3779
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume89
Issue number9
Publication statusPublished - 1992

Fingerprint

Actin Cytoskeleton
Adrenocorticotropic Hormone
Glucocorticoids
Cytochalasins
Corticotrophs
Calmodulin-Binding Proteins
Cytochalasin D
Microfilament Proteins
Cytochalasin B
Membranes
Dexamethasone
Actins
Electron Microscopy
Proteins

Keywords

  • Cytochalasin
  • Exocytosis
  • Pituitary
  • Secretory granules

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Glucocorticoid stabilization of actin filaments : A possible mechanism for inhibition of corticotropin release. / Castellino, Flora; Heuser, John; Marchetti, Sabrina; Bruno, Bernardino; Luini, Alberto.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 89, No. 9, 1992, p. 3775-3779.

Research output: Contribution to journalArticle

Castellino, Flora ; Heuser, John ; Marchetti, Sabrina ; Bruno, Bernardino ; Luini, Alberto. / Glucocorticoid stabilization of actin filaments : A possible mechanism for inhibition of corticotropin release. In: Proceedings of the National Academy of Sciences of the United States of America. 1992 ; Vol. 89, No. 9. pp. 3775-3779.
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