Aunis D, Bader M F
Unité INSERM U44, Centre de Neurochimie, Strasbourg, France.
J Exp Biol. 1988 Sep;139:253-66. doi: 10.1242/jeb.139.1.253.
Chromaffin cells of the adrenal medulla synthesize, store and secrete catecholamines. These cells contain numerous electron-dense secretory granules which discharge their contents into the extracellular space by exocytosis. The subplasmalemmal area of the chromaffin cell is characterized by the presence of a highly organized cytoskeletal network. F-Actin seems to be exclusively localized in this area and together with specific actin-binding proteins forms a dense viscoelastic gel; fodrin, vinculin and caldesmon, three actin cross-linking proteins, and gelsolin, an actin-severing protein, are found in this subplasmalemmal region. Since fodrin-, caldesmon- and alpha-actinin-binding sites exist on secretory granule membranes, actin filaments can also link secretory granules. Chromaffin granules can be entrapped in this subplasmalemmal lattice and thus the cytoskeleton acts as a barrier preventing exocytosis. When cells are stimulated, molecular rearrangements of the subplasmalemmal cytoskeleton take place: F-actin depolymerizes and fodrin reorganizes into patches. In addition, introduction of monospecific antifodrin immunoglobulins into digitonin-permeabilized cells blocks exocytosis, demonstrating the crucial role of this actin-binding protein. In bacterial toxin-permeabilized chromaffin cells, experiments using actin-perturbing agents such as cytochalasin D and DNAase I suggest that exocytosis is in part controlled by the cytoskeleton. The intracellular signal governing the cytoskeletal reorganization (associated with exocytosis) is calcium. Calcium inhibits some and activates other actin-binding proteins and consequently causes dissolution of the subplasmalemmal cytoskeleton. This dissolution of cytoskeletal filaments should result in granule detachment and permit granules free access to exocytotic sites on the plasma membrane.
肾上腺髓质的嗜铬细胞合成、储存和分泌儿茶酚胺。这些细胞含有大量电子致密的分泌颗粒，通过胞吐作用将其内容物释放到细胞外空间。嗜铬细胞的亚膜下区域的特征是存在高度组织化的细胞骨架网络。F-肌动蛋白似乎仅定位于该区域，并与特定的肌动蛋白结合蛋白一起形成致密的粘弹性凝胶；在该亚膜下区域发现了三种肌动蛋白交联蛋白，即血影蛋白、纽蛋白和平滑肌钙结合蛋白，以及一种肌动蛋白切割蛋白凝溶胶蛋白。由于分泌颗粒膜上存在血影蛋白、平滑肌钙结合蛋白和α-辅肌动蛋白的结合位点，肌动蛋白丝也可以连接分泌颗粒。嗜铬颗粒可以被困在这个亚膜下晶格中，因此细胞骨架起到了阻止胞吐作用的屏障作用。当细胞受到刺激时，亚膜下细胞骨架会发生分子重排：F-肌动蛋白解聚，血影蛋白重新组织成斑块。此外，将单特异性抗血影蛋白免疫球蛋白引入洋地黄皂苷通透的细胞中会阻断胞吐作用，证明了这种肌动蛋白结合蛋白的关键作用。在细菌毒素通透的嗜铬细胞中，使用细胞松弛素D和DNA酶I等肌动蛋白干扰剂的实验表明，胞吐作用部分受细胞骨架控制。控制细胞骨架重组（与胞吐作用相关）的细胞内信号是钙。钙抑制一些肌动蛋白结合蛋白并激活其他肌动蛋白结合蛋白，从而导致亚膜下细胞骨架的溶解。细胞骨架丝的这种溶解应导致颗粒脱离，并使颗粒能够自由进入质膜上的胞吐位点。
