GLUCOCORTICOID STABILIZATION OF ACTIN-FILAMENTS - A POSSIBLE MECHANISM FOR INHIBITION OF CORTICOTROPIN RELEASE
GLUCOCORTICOID STABILIZATION OF ACTIN-FILAMENTS - A POSSIBLE MECHANISM FOR INHIBITION OF CORTICOTROPIN RELEASE
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DOI：
10.1073/pnas.89.9.3775
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发表时间：
1992-05-01
影响因子：
11.1
通讯作者：
LUINI, A
中科院分区：
文献类型：
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作者：
CASTELLINO, F;HEUSER, J;LUINI, A
糖皮质激素在不同组织中诱导各种细胞反应的机制仅部分了解。在这里，我们表明，糖皮质激素稳定的肌动蛋白细胞骨架的几种细胞类型，所揭示的增加电阻的肌动蛋白丝的破坏作用的细胞松弛素和可见增厚的肌动蛋白丝束。这些效应需要几个小时的发展，需要蛋白质合成，并伴随着肌动蛋白结合蛋白caldesmon的表达增加。这些数据可能有助于解释为什么糖皮质激素抑制促肾上腺皮质激素从垂体细胞释放，如果解释在目前的想法，肌动蛋白丝的“屏障”调节胞吐分泌在各种类型的细胞。在支持这一想法，我们发现，在“模型”促肾上腺皮质激素（AtT-20细胞），糖皮质激素稳定肌动蛋白丝和抑制促肾上腺皮质激素释放具有类似的效力。此外，我们在这里表明，糖皮质激素的抑制是克服暴露AtT-20细胞的细胞松弛素B或D的浓度，破坏其稳定的肌动蛋白丝。另一方面，我们的AtT-20细胞的冷冻蚀刻电子显微镜显示，肌动蛋白丝，事实上，不创建一个致密的膜下屏障，可能会阻止促肾上腺皮质激素分泌液滴从放电;相反，他们形成开放的网络附近的膜，似乎持有分泌液滴在其间隙。我们建议，微妙的物理交联维持这种肌动蛋白介导的膜“对接”的分泌液滴可能需要断开，以允许促肾上腺皮质激素的排放，这些交联可能是稳定的沿着与地塞米松处理的细胞中的肌动蛋白丝。
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.