The Planar Cell Polarity (PCP) pathway controls multiple cellular processes during vertebrate development. Recently, the PCP pathway was implicated in ciliogenesis and in ciliary function. The primary cilium is an apically-projecting solitary organelle that is generated via polarized intracellular trafficking. Since it acts as a signaling nexus, defects in ciliogenesis or cilial function cause multiple congenital anomalies in vertebrates. Loss of the PCP effector, Fuzzy, affects PCP signaling and formation of primary cilia, however, the mechanisms underlying these processes are largely unknown. In this paper, we report that the PCP effector, Fuzzy, localizes to the basal body and ciliary axoneme and is essentia... More
The Planar Cell Polarity (PCP) pathway controls multiple cellular processes during vertebrate development. Recently, the PCP pathway was implicated in ciliogenesis and in ciliary function. The primary cilium is an apically-projecting solitary organelle that is generated via polarized intracellular trafficking. Since it acts as a signaling nexus, defects in ciliogenesis or cilial function cause multiple congenital anomalies in vertebrates. Loss of the PCP effector, Fuzzy, affects PCP signaling and formation of primary cilia, however, the mechanisms underlying these processes are largely unknown. In this paper, we report that the PCP effector, Fuzzy, localizes to the basal body and ciliary axoneme and is essential for ciliogenesis by delivering Rab8 to the basal body and primary cilium. Fuzzy appears to control subcellular localization of the core PCP protein Dishevelled, recruiting it to Rab8-positive vesicles and to the basal body and cilium. We show that loss of Fuzzy results in inhibition of PCP signaling and hyperactivation of the canonical WNT pathway. Based on our observations, we propose a mechanism whereby Fuzzy participates in ciliogenesis and impacts both canonical WNT and PCP signaling.
