Mesh : Animals Caenorhabditis elegans / metabolism Caenorhabditis elegans Proteins / metabolism genetics Cell Polarity Dystrophin / metabolism genetics Wnt Signaling Pathway Muscles / metabolism Dishevelled Proteins / metabolism genetics Receptor Tyrosine Kinase-like Orphan Receptors / metabolism genetics Cell Membrane / metabolism Dystrophin-Associated Protein Complex / metabolism genetics Wnt Proteins / metabolism Signal Transduction

来  源:   DOI:10.1038/s41467-024-49154-8   PDF(Pubmed)

Abstract:
Cell polarity mechanisms allow the formation of specialized membrane domains with unique protein compositions, signalling properties, and functional characteristics. By analyzing the localization of potassium channels and proteins belonging to the dystrophin-associated protein complex, we reveal the existence of distinct planar-polarized membrane compartments at the surface of C. elegans muscle cells. We find that muscle polarity is controlled by a non-canonical Wnt signalling cascade involving the ligand EGL-20/Wnt, the receptor CAM-1/Ror, and the intracellular effector DSH-1/Dishevelled. Interestingly, classical planar cell polarity proteins are not required for this process. Using time-resolved protein degradation, we demonstrate that -while it is essentially in place by the end of embryogenesis- muscle polarity is a dynamic state, requiring continued presence of DSH-1 throughout post-embryonic life. Our results reveal the unsuspected complexity of the C. elegans muscle membrane and establish a genetically tractable model system to study cellular polarity and membrane compartmentalization in vivo.
摘要:
细胞极性机制允许形成具有独特蛋白质组成的专门膜结构域,信号属性,和功能特征。通过分析钾通道和属于肌营养不良蛋白相关蛋白复合物的蛋白质的定位,我们揭示了在C.elegans肌肉细胞表面存在不同的平面极化膜区室。我们发现,肌肉极性是由涉及配体EGL-20/Wnt的非规范Wnt信号级联控制的,受体CAM-1/Ror,和细胞内效应物DSH-1/Dishevelled。有趣的是,此过程不需要经典的平面细胞极性蛋白。使用时间分辨的蛋白质降解,我们证明了-虽然它在胚胎发生结束时基本上已经到位-肌肉极性是一种动态状态,需要在整个胚胎后生命中持续存在DSH-1。我们的结果揭示了C.elegans肌肉膜的意外复杂性,并建立了一个可遗传处理的模型系统来研究体内细胞极性和膜区室化。
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