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Domains are demarcated by structural features such as the axoneme and its connections to the ciliary membrane, and are correlated with molecular markers of subcompartments, including the lumen and walls of the axoneme, the membrane glycocalyx, and the intervening cytoplasm. 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Sung, Ultrastructural visualization of trans-ciliary rhodopsin cargoes in mammalian rods. Cilia 4, 4 (2015).","journal-title":"Cilia"},{"key":"e_1_3_4_49_2","doi-asserted-by":"crossref","first-page":"1028","DOI":"10.1016\/j.cell.2016.06.016","article-title":"Ultra-high resolution 3D imaging of whole cells","volume":"166","author":"Huang F.","year":"2016","unstructured":"F. Huang ., Ultra-high resolution 3D imaging of whole cells. Cell 166, 1028\u20131040 (2016).","journal-title":"Cell"},{"key":"e_1_3_4_50_2","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1016\/j.bpj.2018.11.3136","article-title":"Revealing nanoscale morphology of the primary cilium using super-resolution fluorescence microscopy","volume":"116","author":"Yoon J.","year":"2019","unstructured":"J. Yoon ., Revealing nanoscale morphology of the primary cilium using super-resolution fluorescence microscopy. Biophys. J. 116, 319\u2013329 (2019).","journal-title":"Biophys. J."},{"key":"e_1_3_4_51_2","doi-asserted-by":"crossref","first-page":"1250","DOI":"10.1038\/s41556-018-0213-1","article-title":"The cryo-EM structure of intraflagellar transport trains reveals how dynein is inactivated to ensure unidirectional anterograde movement in cilia","volume":"20","author":"Jordan M. A.","year":"2018","unstructured":"M. A. Jordan, D. R. Diener, L. Stepanek, G. Pigino, The cryo-EM structure of intraflagellar transport trains reveals how dynein is inactivated to ensure unidirectional anterograde movement in cilia. Nat. Cell Biol. 20, 1250\u20131255 (2018).","journal-title":"Nat. Cell Biol."},{"key":"e_1_3_4_52_2","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1083\/jcb.200905103","article-title":"Electron-tomographic analysis of intraflagellar transport particle trains in situ","volume":"187","author":"Pigino G.","year":"2009","unstructured":"G. Pigino ., Electron-tomographic analysis of intraflagellar transport particle trains in situ. J. Cell Biol. 187, 135\u2013148 (2009).","journal-title":"J. Cell Biol."},{"key":"e_1_3_4_53_2","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1083\/jcb.144.3.385","article-title":"Intraflagellar transport: The eyes have it","volume":"144","author":"Rosenbaum J. L.","year":"1999","unstructured":"J. L. Rosenbaum, D. G. Cole, D. R. Diener, Intraflagellar transport: The eyes have it. J. Cell Biol. 144, 385\u2013388 (1999).","journal-title":"J. Cell Biol."},{"key":"e_1_3_4_54_2","doi-asserted-by":"crossref","first-page":"1178","DOI":"10.1038\/ncb3599","article-title":"Super-resolution microscopy reveals that disruption of ciliary transition-zone architecture causes Joubert syndrome","volume":"19","author":"Shi X.","year":"2017","unstructured":"X. Shi ., Super-resolution microscopy reveals that disruption of ciliary transition-zone architecture causes Joubert syndrome. Nat. Cell Biol. 19, 1178\u20131188 (2017).","journal-title":"Nat. Cell Biol."},{"key":"e_1_3_4_55_2","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1016\/j.bpj.2018.04.051","article-title":"Super-resolution imaging reveals TCTN2 depletion-induced IFT88 lumen leakage and ciliary weakening","volume":"115","author":"Weng R. R.","year":"2018","unstructured":"R. R. Weng ., Super-resolution imaging reveals TCTN2 depletion-induced IFT88 lumen leakage and ciliary weakening. Biophys. J. 115, 263\u2013275 (2018).","journal-title":"Biophys. J."},{"key":"e_1_3_4_56_2","doi-asserted-by":"crossref","first-page":"34211","DOI":"10.1074\/jbc.M300156200","article-title":"IFT20 links kinesin II with a mammalian intraflagellar transport complex that is conserved in motile flagella and sensory cilia","volume":"278","author":"Baker S. A.","year":"2003","unstructured":"S. A. Baker, K. Freeman, K. Luby-Phelps, G. J. Pazour, J. C. Besharse, IFT20 links kinesin II with a mammalian intraflagellar transport complex that is conserved in motile flagella and sensory cilia. J. Biol. Chem. 278, 34211\u201334218 (2003).","journal-title":"J. Biol. Chem."},{"key":"e_1_3_4_57_2","doi-asserted-by":"crossref","first-page":"1117","DOI":"10.1083\/jcb.200909183","article-title":"The Chlamydomonas reinhardtii BBSome is an IFT cargo required for export of specific signaling proteins from flagella","volume":"187","author":"Lechtreck K. F.","year":"2009","unstructured":"K. F. Lechtreck ., The Chlamydomonas reinhardtii BBSome is an IFT cargo required for export of specific signaling proteins from flagella. J. Cell Biol. 187, 1117\u20131132 (2009).","journal-title":"J. Cell Biol."},{"key":"e_1_3_4_58_2","doi-asserted-by":"crossref","first-page":"20625","DOI":"10.1074\/jbc.M112.341487","article-title":"Intrinsic protein-protein interaction-mediated and chaperonin-assisted sequential assembly of stable Bardet-Biedl syndrome protein complex, the BBSome","volume":"287","author":"Zhang Q.","year":"2012","unstructured":"Q. Zhang, D. Yu, S. Seo, E. M. Stone, V. C. Sheffield, Intrinsic protein-protein interaction-mediated and chaperonin-assisted sequential assembly of stable Bardet-Biedl syndrome protein complex, the BBSome. J. Biol. Chem. 287, 20625\u201320635 (2012).","journal-title":"J. Biol. Chem."},{"key":"e_1_3_4_59_2","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1093\/hmg\/ddx399","article-title":"Bardet-Biedl syndrome-8 (BBS8) protein is crucial for the development of outer segments in photoreceptor neurons","volume":"27","author":"Dilan T. L.","year":"2018","unstructured":"T. L. Dilan ., Bardet-Biedl syndrome-8 (BBS8) protein is crucial for the development of outer segments in photoreceptor neurons. Hum. Mol. Genet. 27, 283\u2013294 (2018).","journal-title":"Hum. Mol. Genet."},{"key":"e_1_3_4_60_2","doi-asserted-by":"crossref","first-page":"9583","DOI":"10.1038\/srep09583","article-title":"Correlative in-resin super-resolution and electron microscopy using standard fluorescent proteins","volume":"5","author":"Johnson E.","year":"2015","unstructured":"E. Johnson ., Correlative in-resin super-resolution and electron microscopy using standard fluorescent proteins. Sci. Rep. 5, 9583 (2015). Erratum in: Sci. Rep. 6, 22681 (2016).","journal-title":"Sci. Rep."},{"key":"e_1_3_4_61_2","doi-asserted-by":"crossref","first-page":"e0124581","DOI":"10.1371\/journal.pone.0124581","article-title":"Correlative stochastic optical reconstruction microscopy and electron microscopy","volume":"10","author":"Kim D.","year":"2015","unstructured":"D. Kim ., Correlative stochastic optical reconstruction microscopy and electron microscopy. PLoS One 10, e0124581 (2015).","journal-title":"PLoS One"},{"key":"e_1_3_4_62_2","volume-title":"Guide for the Care and Use of Laboratory Animals","author":"National Research Council","year":"2011","unstructured":"National Research Council, Guide for the Care and Use of Laboratory Animals (National Academies Press, Washington, DC, ed. 8, 2011).","edition":"8"},{"key":"e_1_3_4_63_2","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1038\/nmeth.2472","article-title":"Electron counting and beam-induced motion correction enable near-atomic-resolution single-particle cryo-EM","volume":"10","author":"Li X.","year":"2013","unstructured":"X. Li ., Electron counting and beam-induced motion correction enable near-atomic-resolution single-particle cryo-EM. Nat. Methods 10, 584\u2013590 (2013).","journal-title":"Nat. Methods"},{"key":"e_1_3_4_64_2","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1006\/jsbi.1996.0013","article-title":"Computer visualization of three-dimensional image data using IMOD","volume":"116","author":"Kremer J. R.","year":"1996","unstructured":"J. R. Kremer, D. N. Mastronarde, J. R. McIntosh, Computer visualization of three-dimensional image data using IMOD. J. Struct. Biol. 116, 71\u201376 (1996).","journal-title":"J. Struct. Biol."},{"key":"e_1_3_4_65_2","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1016\/j.jsb.2016.07.011","article-title":"Automated tilt series alignment and tomographic reconstruction in IMOD","volume":"197","author":"Mastronarde D. N.","year":"2017","unstructured":"D. N. Mastronarde, S. R. Held, Automated tilt series alignment and tomographic reconstruction in IMOD. J. Struct. Biol. 197, 102\u2013113 (2017).","journal-title":"J. Struct. Biol."},{"key":"e_1_3_4_66_2","doi-asserted-by":"crossref","first-page":"1605","DOI":"10.1002\/jcc.20084","article-title":"UCSF Chimera\u2014A visualization system for exploratory research and analysis","volume":"25","author":"Pettersen E. F.","year":"2004","unstructured":"E. F. Pettersen ., UCSF Chimera\u2014A visualization system for exploratory research and analysis. J. Comput. Chem. 25, 1605\u20131612 (2004).","journal-title":"J. Comput. Chem."},{"key":"e_1_3_4_67_2","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.jsb.2006.05.009","article-title":"EMAN2: An extensible image processing suite for electron microscopy","volume":"157","author":"Tang G.","year":"2007","unstructured":"G. Tang ., EMAN2: An extensible image processing suite for electron microscopy. J. Struct. Biol. 157, 38\u201346 (2007).","journal-title":"J. Struct. 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