Par3A and Par3B orchestrate podocyte architecture by regulating RhoA levels
Par3A and Par3B orchestrate podocyte architecture by regulating RhoA levels
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DOI：
10.1101/2020.02.10.933671
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发表时间：
2020-02
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通讯作者：
Sybille Koehler;Johanna Odenthal;David Unnersjö Jess;M. Höhne;C. Jüngst;F. Grawe;M. Helmstädter;H. Hagmann;G. Walz;W. Bloch;C. Niessen;B. Schermer;A. Wodarz;B. Denholm;T. Benzing;S. Iden;P. Brinkkoetter
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作者：
Sybille Koehler;Johanna Odenthal;David Unnersjö Jess;M. Höhne;C. Jüngst;F. Grawe;M. Helmstädter;H. Hagmann;G. Walz;W. Bloch;C. Niessen;B. Schermer;A. Wodarz;B. Denholm;T. Benzing;S. Iden;P. Brinkkoetter
肾小球疾病是慢性肾脏疾病的主要原因。在大多数情况下，足细胞损伤是疾病发展的原因。细胞骨架重排和形态学变化是足细胞损伤的标志性特征，并导致足细胞的去分化和随后的损失。在这里，我们建立了Par 3极性复合物和肌动蛋白调节剂，这是必要的建立和维持足细胞的架构，利用两个，小鼠和果蝇模型的组件之间的联系。我们证明，两种哺乳动物的Par 3蛋白，Par 3A和Par 3B，共享冗余的功能，尽管他们的能力不同，与其他组件的Par复合物。只有同时失活的两个Par 3蛋白导致一个严重的疾病表型，在小鼠足细胞通过调节Rho-GTP水平，涉及肌动蛋白调节剂突触足蛋白和CD 2AP在一个aPKC独立的方式。
Glomerular diseases are a major cause for chronic kidney disorders. In the majority of cases podocyte injury is causative for disease development. Cytoskeletal rearrangements and morphological changes are hallmark features of podocyte injury and result in dedifferentiation and subsequent loss of podocytes. Here, we establish a link between components of the Par3 polarity complex and actin regulators, which are necessary to establish and maintain the podocytes architecture utilizing both, mouse and Drosophila models. We demonstrate that the two mammalian Par3 proteins, Par3A and Par3B, share redundant functions despite differing in their ability to interact with other components of the Par complex. Only simultaneous inactivation of both Par3 proteins causes a severe disease phenotype in mouse podocytes by regulating Rho-GTP levels involving the actin regulators Synaptopodin and CD2AP in an aPKC independent manner.