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快乐十分前三组常出好:Three-dimensional architecture of epithelial primary cilia
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Primary cilia are sensory organelles that detect a wide range of extracellular signals for regulation of cell proliferation. Defects of their assembly/disassembly (primary ciliogenesis) and maintenance are linked to a variety of medical disorders. The signals they detect include mechano-signals from liquid flow, which requires a reversible bending property of the primary cilium axoneme. An accurate 3D structure of primary cilia is essential to fully understand the process and regulation of primary ciliogenesis and clarify the structural basis of the elastic bending property. Here we report complete 3D structural maps and a model for typical epithelial primary cilia, which will serve as the updated structural base for studies of primary cilium assembly and regulation, and mechanosensory function.
We report a complete 3D structural model of typical epithelial primary cilia based on structural maps of full-length primary cilia obtained by serial section electron tomography. Our data demonstrate the architecture of primary cilia differs extensively from the commonly acknowledged 9+0 paradigm. The axoneme structure is relatively stable but gradually evolves from base to tip with a decreasing number of microtubule complexes (MtCs) and a reducing diameter. The axonemal MtCs are cross-linked by previously unrecognized fibrous protein networks. Such an architecture explains why primary cilia can elastically withstand liquid flow for mechanosensing. The nine axonemal MtCs in a cilium are found to differ significantly in length indicating intraflagellar transport processes in primary cilia may be more complicated than that reported for motile cilia. The 3D maps of microtubule doublet–singlet transitions generally display longitudinal gaps at the inner junction between the A- and B-tubules, which indicates the inner junction protein is a major player in doublet–singlet transitions. In addition, vesicles releasing from kidney primary cilia were observed in the structural maps, supporting that ciliary vesicles budding may serve as ectosomes for cell–cell communication.
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Author contributions: H.S. designed research; S.S., R.L.F., and H.S. performed research; S.S.B., B.T.P., and H.S. contributed new reagents/analytic tools; S.S. and H.S. analyzed data; and S.S., B.T.P., and H.S. wrote the paper.
The authors declare no conflict of interest.
This article is a PNAS Direct Submission.
Data deposition: The 3D structural maps of the primary cilia in this study are available in the Electron Microscopy Data Bank, https://www.ebi.ac.uk/ (accession nos. EMD-9022, EMD-20061, EMD-20064–EMD-20068).
This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1821064116/-/DCSupplemental.
Published under the PNAS license.