{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T15:13:34Z","timestamp":1783350814706,"version":"3.54.6"},"reference-count":63,"publisher":"National Academy of Sciences","issue":"49","license":[{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"MEXT | Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP19K06560"],"award-info":[{"award-number":["JP19K06560"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"MEXT | Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP21H05307"],"award-info":[{"award-number":["JP21H05307"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006680","name":"Takeda Medical Research Foundation","doi-asserted-by":"publisher","award":["No.1"],"award-info":[{"award-number":["No.1"]}],"id":[{"id":"10.13039\/501100006680","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2025,12,9]]},"abstract":"<jats:p>\n                    Cilia are hair-like organelles that protrude from the cell surface. In mammals, tracheal multiciliated cells (MCCs) play an important role in elimination of hazardous microorganisms by driving a unidirectional mucus flow. Although uniform orientation of ciliary beating is critical for the unidirectional flow, it remains unknown how MCCs establish uniform orientations and maintain identities of hundreds of ciliary membranes. This study focuses on investigating the roles of Tubulin Polymerization Promoting Family Member 3 (Tppp3) in MCC function. We generated a Tppp3-deficient mouse (\n                    <jats:italic toggle=\"yes\">Tppp3<\/jats:italic>\n                    <jats:sup>\u2206ex2-4\/\u2206ex2-4<\/jats:sup>\n                    ;\n                    <jats:italic toggle=\"yes\">Tppp3<\/jats:italic>\n                    knockout (KO)) and found that the\n                    <jats:italic toggle=\"yes\">Tppp3<\/jats:italic>\n                    KO mouse exhibited cough and hyposmia phenotype. The loss of Tppp3 disrupted the apical microtubules (MTs) meshwork in the tracheal MCCs, leading to random orientation and alignment of basal bodies (BBs) of the motile cilia. Unexpectedly, aberrant ciliary membrane fusions occurred in the trachea of the\n                    <jats:italic toggle=\"yes\">Tppp3<\/jats:italic>\n                    KO mice. We examined the underlying molecular mechanism of the ciliary membrane fusion by isolating the tracheal cilium. Liquid Chromatography-Mass Spectrometry (LC\u2013MS) analysis as well as pharmacological analysis revealed that hyperaccumulation of a long chain ceramide at the ciliary membrane caused the membrane fusion. In addition, sensory cilia formation was impaired in the olfactory sensory neuron of the\n                    <jats:italic toggle=\"yes\">Tppp3<\/jats:italic>\n                    KO mice. Due to the lack of Tppp3, dendritic MT assembly that underlies long-range migration of BBs toward the cell surface was impaired. These findings demonstrate that Tppp3, as well as the defined intracellular MT architecture, regulate proper orientation\/subcellular positioning of BBs and the independency of individual motile cilium membranes.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2503931122","type":"journal-article","created":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T20:00:36Z","timestamp":1764619236000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":1,"title":["Tppp3 determines basal body positioning and identity of respiratory cilia via microtubule assembly and sphingolipid homeostasis"],"prefix":"10.1073","volume":"122","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-9533-6909","authenticated-orcid":false,"given":"Takafumi","family":"Sakai","sequence":"first","affiliation":[{"name":"Department of Biotechnology and Life Science, Tokyo University of Agriculture and Technology","place":["Tokyo, Koganei, 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