Author: ["Daqing Jin","Terri T. Ni","Jianjian Sun","Haiyan Wan","Jeffrey D. Amack","Guangju Yu","Jonathan Fleming","Chin Chiang","Wenyan Li","Anna Papierniak","Satish Cheepala","Gwenaëlle Conseil","Susan P. C. Cole","Bin Zhou","Iain A. Drummond","John D. Schuetz","Jarema Malicki","Tao P. Zhong"]
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Abstract
Cilia are microtubule-based organelles that mediate signal transduction in a variety of tissues. Despite their importance, the signalling cascades that regulate cilium formation remain incompletely understood. Here we report that prostaglandin signalling affects ciliogenesis by regulating anterograde intraflagellar transport (IFT). Zebrafish leakytail (lkt) mutants show ciliogenesis defects, and the lkt locus encodes an ATP-binding cassette transporter (ABCC4). We show that Lkt/ABCC4 localizes to the cell membrane and exports prostaglandin E2 (PGE2), a function that is abrogated by the Lkt/ABCC4T804M mutant. PGE2 synthesis enzyme cyclooxygenase-1 and its receptor, EP4, which localizes to the cilium and activates the cyclic-AMP-mediated signalling cascade, are required for cilium formation and elongation. Importantly, PGE2 signalling increases anterograde but not retrograde velocity of IFT and promotes ciliogenesis in mammalian cells. These findings lead us to propose that Lkt/ABCC4-mediated PGE2 signalling acts through a ciliary G-protein-coupled receptor, EP4, to upregulate cAMP synthesis and increase anterograde IFT, thereby promoting ciliogenesis. Zhong and colleagues report that zebrafish leakytail (Lkt) promotes ciliogenesis by exporting prostaglandin E2 to upregulate cAMP synthesis. A human orthologue of Lkt, ABCC4, is also important for ciliogenesis in human retinal pigment epithelial cells.Cite this article
Jin, D., Ni, T., Sun, J. et al. Prostaglandin signalling regulates ciliogenesis by modulating intraflagellar transport. Nat Cell Biol 16, 841–851 (2014). https://doi.org/10.1038/ncb3029 