Norman J C, Price L S, Ridley A J, Koffer A
Physiology Department, University College London, United Kingdom.
Mol Biol Cell. 1996 Sep;7(9):1429-42. doi: 10.1091/mbc.7.9.1429.
In mast cells, activation of GTP-binding proteins induces centripetal reorganization of actin filaments. This effect is due to disassembly, relocalization, and polymerization of F-actin and is dependent on two small GTPases, Rac and Rho. Activities of Rac and Rho are also essential for the secretory function of mast cells. In response to GTP-gamma-S and/or calcium, only a proportion of permeabilized mast cells is capable of secretory response. Here, we have compared actin organization of secreting and nonsecreting cell populations. We show that the cytoskeletal and secretory responses are strongly correlated, indicating a common upstream regulator of the two functions. The secreting cell population preferentially displays both relocalization and polymerization of actin. However, when actin relocalization or polymerization is inhibited by phalloidin or cytochalasin, respectively, secretion is unaffected. Moreover, the ability of the constitutively active mutants of Rac and Rho to enhance secretion is also unaffected in the presence of cytochalasin. Therefore, Rac and Rho control these two functions by divergent, parallel signaling pathways. Cortical actin disassembly occurs in both secreting and nonsecreting populations and does not, by itself, induce exocytosis. A model for the control of exocytosis is proposed that includes at least four GTP-binding proteins and suggests the presence of both shared and divergent signaling pathways from Rac and Rho.
在肥大细胞中，GTP结合蛋白的激活会诱导肌动蛋白丝向心重排。这种效应是由于F-肌动蛋白的解聚、重新定位和聚合，并且依赖于两种小GTP酶，即Rac和Rho。Rac和Rho的活性对于肥大细胞的分泌功能也至关重要。在对GTP-γ-S和/或钙作出反应时，只有一部分通透的肥大细胞能够产生分泌反应。在此，我们比较了分泌性和非分泌性细胞群体的肌动蛋白组织。我们发现细胞骨架反应和分泌反应密切相关，这表明这两种功能有一个共同的上游调节因子。分泌性细胞群体优先表现出肌动蛋白的重新定位和聚合。然而，当分别用鬼笔环肽或细胞松弛素抑制肌动蛋白的重新定位或聚合时，分泌不受影响。此外，在存在细胞松弛素的情况下，Rac和Rho的组成型活性突变体增强分泌的能力也不受影响。因此，Rac和Rho通过不同的平行信号通路控制这两种功能。皮质肌动蛋白解聚在分泌性和非分泌性群体中都会发生，但其本身并不会诱导胞吐作用。我们提出了一个胞吐作用控制模型，该模型至少包括四种GTP结合蛋白，并表明存在来自Rac和Rho的共享和不同的信号通路。
