Seamless tube shape is constrained by endocytosis-dependent regulation of active Moesin.
Seamless tube shape is constrained by endocytosis-dependent regulation of active Moesin.
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DOI：
10.1016/j.cub.2014.06.029
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发表时间：
2014-08-04
期刊：
影响因子：
9.2
通讯作者：
Ghabrial, Amin S.
中科院分区：
文献类型：
--
作者：
Schottenfeld-Roames, Jodi;Rosa, Jeffrey B.;Ghabrial, Amin S.
大多数管有“接缝”-细胞间或自体细胞连接，将膜密封在一起形成管-但也存在“无缝”管。在果蝇中，星状的气管末端细胞形成无缝的管道，单个分支贯穿数十个细胞延伸的每一个。我们发现，在编织突变损害终端细胞的分支，并导致形成无缝管囊肿。我们发现，编织编码Syntaxin 7，并且在缺乏膜断裂（shibire）或早期内体形成（Rab 5，Vps 45和Rabenosyn-5）所需的其他基因的细胞中也形成包囊。这些数据定义了在成形无缝管腔时对早期内吞作用的要求。重要的是，顶端蛋白Crumbs和磷酸化膜突蛋白在编织终末细胞中积累到异常高的水平。过表达的Crumbs，或磷酸模拟Moesin，诱导管腔囊肿和减少终端分支。相反，编织的无缝管囊肿表型被抑制的突变碎屑或Moesin。事实上，Moesin的突变主要抑制无缝管囊肿形成并恢复末端分支。我们建议，早期的内吞作用保持正常的稳态水平的碎屑，招募顶端的p-Moe，这反过来又调节无缝管的形状，通过调制皮层肌动蛋白丝。
Most tubes have “seams” – intercellular or autocellular junctions that seal membranes together into a tube – but “seamless” tubes also exist. In Drosophila, stellate-shaped tracheal terminal cells make seamless tubes, with single branches running through each of dozens of cellular extensions. We find that mutations in braided impair terminal cell branching and cause formation of seamless tube cysts. We show that braided encodes Syntaxin7, and that cysts also form in cells deficient for other genes required either for membrane scission (shibire), or for early endosome formation (Rab5, Vps45, and Rabenosyn-5). These data define a requirement for early endocytosis in shaping seamless tube lumens. Importantly, apical proteins Crumbs and phospho-Moesin accumulate to aberrantly high levels in braided terminal cells. Overexpression of either Crumbs, or phospho-mimetic Moesin, induced lumenal cysts and decreased terminal branching. Conversely, the braided seamless tube cyst phenotype was suppressed by mutations in crumbs or Moesin. Indeed, mutations in Moesin dominantly suppressed seamless tube cyst formation and restored terminal branching. We propose that early endocytosis maintains normal steady-state levels of Crumbs, which recruits apical p-Moe, which in turn regulates seamless tube shape through modulation of cortical actin filaments.
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