Cdc42 negatively regulates endocytosis during apical membrane maintenance in live animals
Cdc42 negatively regulates endocytosis during apical membrane maintenance in live animals
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DOI：
10.1091/mbc.e18-10-0615
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发表时间：
2019-02-01
影响因子：
3.3
通讯作者：
Weigert, Roberto
中科院分区：
文献类型：
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作者：
Shitara, Akiko;Malec, Lenka;Weigert, Roberto
管腔的建立和维持是肾小管器官生理功能的基础。大多数关于调控这一过程的机制的研究都是在细胞培养或较小的生物体中进行的，而在活体的哺乳动物模型系统中进行的研究很少。在这里，我们使用活着的小鼠的唾液腺来研究小GTP酶CDC42在细胞间小管内稳态调节中的作用，细胞间小管是腺泡细胞的一个专门的顶端区域，在那里发生蛋白质和液体的分泌。在成年小鼠中，Cdc42的耗尽导致顶管的显著扩张，而在胚胎晚期的耗尽导致其出生后的形成完全被抑制。此外，活体亚细胞显微镜显示，CDC42水平的降低影响了从质膜到质膜的膜运输，突显了CDC42通过对选定的内吞途径进行负性调节而在膜重塑中的新作用。
Lumen establishment and maintenance are fundamental for tubular organs physiological functions. Most of the studies investigating the mechanisms regulating this process have been carried out in cell cultures or in smaller organisms, whereas little has been done in mammalian model systems in vivo. Here we used the salivary glands of live mice to examine the role of the small GTPase Cdc42 in the regulation of the homeostasis of the intercellular canaliculi, a specialized apical domain of the acinar cells, where protein and fluid secretion occur. Depletion of Cdc42 in adult mice induced a significant expansion of the apical canaliculi, whereas depletion at late embryonic stages resulted in a complete inhibition of their postnatal formation. In addition, intravital subcellular microscopy revealed that reduced levels of Cdc42 affected membrane trafficking from and toward the plasma membrane, highlighting a novel role for Cdc42 in membrane remodeling through the negative regulation of selected endocytic pathways.