Septin 9 Orients the Apico-Basal Polarity Axis and Controls Plasticity Signals Septin 9 Orients the Apico-Basal Polarity Axis and Controls Plasticity Signals

卷:12

Article

关键词: TYROSINE PHOSPHORYLATION;    CELL POLARITY;    CORTACTIN;    CYTOSKELETON;    PROTEINS;    SRC;    CILIOGENESIS;    GENERATION;    REGULATOR;    MIGRATION;   

DOI  :  10.3390/cells12141815

来源: SCIE

【 摘 要 】

The cytoskeleton is a master organizer of the cellular cortex and membrane trafficking and therefore plays a crucial role in apico-basal polarity. Septins form a family of GTPases that assemble into non-polar filaments, which bind to membranes and recruit cytoskeletal elements such as microtubules and actin using their polybasic (PB) domains, to perform their broad biological functions. Nevertheless, the role of septins and the significance of their membrane-binding ability in apico-basal polarity remains under-investigated. Here, using 3D cultures, we demonstrated that septin 9 localizes to the basolateral membrane (BM). Its depletion induces an inverted polarity phenotype, decreasing beta-catenin at BM and increasing transforming growth factor (TGF beta) and Epithelial-Mesenchymal Transition (EMT) markers. Similar effects were observed after deleting its two PB domains. The mutant became cytoplasmic and apical. The cysts with an inverted polarity phenotype displayed an invasive phenotype, with src and cortactin accumulating at the peripheral membrane. The inhibition of TGF beta-receptor and RhoA rescued the polarized phenotype, although the cysts from overexpressed septin 9 overgrew and presented a filled lumen. Both phenotypes corresponded to tumor features. This suggests that septin 9 expression, along with its assembly through the two PB domains, is essential for establishing and maintaining apico-basal polarity against tumor development.