Cdc42 negatively regulates endocytosis during apical plasma membrane maintenance and development in mouse tubular organs in vivo
Cdc42 negatively regulates endocytosis during apical plasma membrane maintenance and development in mouse tubular organs in vivo
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Cdc42在体内小鼠管状器官顶端质膜维持和发育过程中负向调节内吞作用
DOI：
10.1101/402677
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发表时间：
2018
期刊：
影响因子：
--
通讯作者：
Weigert Roberto
中科院分区：
文献类型：
--
作者：
Shitara Akiko;Malec Lenka;Ebrahim Seham;Chen Desu;Bleck Christopher;Hoffman Matthew P;Weigert Roberto
管腔的建立和维持是管状器官生理功能的基础。大多数研究都是在细胞培养或较小的生物体中进行的，而很少在哺乳动物模型系统中进行。在这里，我们用活小鼠的唾液腺检查的作用，小GTdR Cdc42在调节的细胞间小管，一个专门的顶端域的腺泡细胞，蛋白质和液体分泌发生的稳态。耗尽Cdc42在成年小鼠诱导的顶小管的显着扩张，而在胚胎晚期耗尽导致其出生后形成的完全抑制。此外，活体亚细胞显微镜检查显示，Cdc42水平降低影响膜运输和朝向质膜，突出了Cdc42在膜重塑中通过所选内吞途径的负调节的新作用。
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 systemsin 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 post-natal formation. In addition, intravital subcellular microscopy revealed that reduced levels of Cdc42 affected membrane trafficking from and towards the plasma membrane, highlighting a novel role for Cdc42 in membrane remodeling through the negative regulation of selected endocytic pathways.