Bicaudal C, a novel regulator of Dvl signaling abutting RNA-processing bodies, controls cilia orientation and leftward flow.
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.
Pubmed ID: 19666828 RIS Download
Adaptor Proteins, Signal Transducing | Animals | Body Patterning | Carrier Proteins | Cell Line | Cell Polarity | Cilia | Embryo, Mammalian | Humans | Mice | Mice, Inbred C57BL | Mice, Knockout | Nodal Protein | Phosphoproteins | RNA Interference | RNA-Binding Proteins | Signal Transduction | Wnt Proteins | Xenopus laevis