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We report here that the beating asymmetry is crucial for ciliary function and requires tubulin glutamylation, a unique posttranslational modification that is highly abundant in cilia. WT murine tracheal cilia have an axoneme-intrinsic structural curvature that points in the direction of effective strokes. The axonemal curvature was lost in tracheal cilia from mice with knockout of a tubulin glutamylation-performing enzyme, tubulin tyrosine ligase-like protein 1. Along with the loss of axonemal curvature, the axonemes and tracheal epithelial cilia from these knockout (KO) mice lost beating asymmetry. The loss of beating asymmetry resulted in a reduction of cilia-generated fluid flow in trachea from the KO mice. The KO mice displayed a significant accumulation of mucus in the nasal cavity, and also emitted frequent coughing- or sneezing-like noises. Thus, the beating asymmetry is important for airway ciliary function. Our find-ings provide evidence that tubulin glutamylation is essential for ciliary function through the regulation of beating asymmetry, and provides insight into the molecular basis underlying the beating asymmetry.<\/jats:p>","DOI":"10.1073\/pnas.1002128107","type":"journal-article","created":{"date-parts":[[2010,5,24]],"date-time":"2010-05-24T23:59:42Z","timestamp":1274745582000},"page":"10490-10495","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":169,"title":["Tubulin polyglutamylation is essential for airway ciliary function through the regulation of beating asymmetry"],"prefix":"10.1073","volume":"107","author":[{"given":"Koji","family":"Ikegami","sequence":"first","affiliation":[{"name":"Department of Molecular Anatomy, Molecular Imaging Advanced Research Center, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka 431-3192, Japan;"},{"name":"Mitsubishi Kagaku Institute of Life Sciences, Machida, Tokyo 194-8511, Japan; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Showbu","family":"Sato","sequence":"additional","affiliation":[{"name":"Mitsubishi Kagaku Institute of Life Sciences, Machida, Tokyo 194-8511, Japan; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenji","family":"Nakamura","sequence":"additional","affiliation":[{"name":"Mitsubishi Kagaku Institute of Life Sciences, Machida, Tokyo 194-8511, Japan; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lawrence E.","family":"Ostrowski","sequence":"additional","affiliation":[{"name":"Cystic Fibrosis\/Pulmonary Research and Treatment Center, University of North Carolina, Chapel Hill, NC 27599"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitsutoshi","family":"Setou","sequence":"additional","affiliation":[{"name":"Department of Molecular Anatomy, Molecular Imaging Advanced Research Center, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka 431-3192, Japan;"},{"name":"Mitsubishi Kagaku Institute of Life Sciences, Machida, Tokyo 194-8511, Japan; and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2010,5,24]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.11.1.179"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1084576"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1053\/j.semperi.2005.11.001"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1159\/000101783"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1128618"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature04816"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1967194"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.88.11.4685"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1113010"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M603984200"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0611547104"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2007.04.012"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1247\/csf.09027"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2009.06.003"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1128\/EC.00176-09"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.112.23.4357"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.109.6.1545"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-9822(00)00767-3"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1128\/EC.00084-08"},{"key":"e_1_3_3_20_2","first-page":"425","article-title":"Distribution of glutamylated \u03b1 and \u03b2-tubulin in mouse tissues using a specific monoclonal antibody, GT335","volume":"59","author":"Wolff A","year":"1992","unstructured":"A Wolff, et al., Distribution of glutamylated \u03b1 and \u03b2-tubulin in mouse tissues using a specific monoclonal antibody, GT335. 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