Maisonneuve Charlotte, Guilleret Isabelle, Vick Philipp, Weber Thomas, Andre Philipp, Beyer Tina, Blum Martin, Constam Daniel B
Ecole Polytechnique Fédérale de Lausanne, Station 19, Lausanne, Switzerland.
Development. 2009 Sep;136(17):3019-30. doi: 10.1242/dev.038174.
Polycystic diseases and left-right (LR) axis malformations are frequently linked to cilia defects. Renal cysts also arise in mice and frogs lacking Bicaudal C (BicC), a conserved RNA-binding protein containing K-homology (KH) domains and a sterile alpha motif (SAM). However, a role for BicC in cilia function has not been demonstrated. Here, we report that targeted inactivation of BicC randomizes left-right (LR) asymmetry by disrupting the planar alignment of motile cilia required for cilia-driven fluid flow. Furthermore, depending on its SAM domain, BicC can uncouple Dvl2 signaling from the canonical Wnt pathway, which has been implicated in antagonizing planar cell polarity (PCP). The SAM domain concentrates BicC in cytoplasmic structures harboring RNA-processing bodies (P-bodies) and Dvl2. These results suggest a model whereby BicC links the orientation of cilia with PCP, possibly by regulating RNA silencing in P-bodies.
多囊性疾病和左右（LR）轴畸形常常与纤毛缺陷有关。在缺乏双尾C（BicC）的小鼠和青蛙中也会出现肾囊肿，BicC是一种保守的RNA结合蛋白，含有K-同源（KH）结构域和一个无活性α基序（SAM）。然而，BicC在纤毛功能中的作用尚未得到证实。在这里，我们报告说，BicC的靶向失活通过破坏纤毛驱动的流体流动所需的运动纤毛的平面排列，使左右（LR）不对称随机化。此外，根据其SAM结构域，BicC可以使Dvl2信号与经典Wnt信号通路解偶联，该通路与拮抗平面细胞极性（PCP）有关。SAM结构域将BicC集中在含有RNA加工小体（P小体）和Dvl2的细胞质结构中。这些结果提示了一个模型，即BicC可能通过调节P小体中的RNA沉默，将纤毛的方向与PCP联系起来。
