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Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2025,1,21]]},"abstract":"<jats:p>\n                    Tubulin detyrosination has been implicated in various human disorders and is important for regulating microtubule dynamics. While in most organisms this modification is restricted to \u03b1-tubulin, in trypanosomatid parasites, it occurs on both \u03b1- and \u03b2-tubulin. Here, we show that in\n                    <jats:italic>Leishmania<\/jats:italic>\n                    , a single vasohibin (LmVASH) enzyme is responsible for differential kinetics of \u03b1- and \u03b2-tubulin detyrosination. LmVASH knockout parasites, which are completely devoid of detyrosination, show decreased levels of glutamylation and exhibit a strongly diminished pathogenicity in mice, correlating with decreased proliferation in macrophages. Reduced virulence is associated with altered morphogenesis and flagellum remodeling in detyrosination-deficient amastigotes. Flagellum shortening in the absence of detyrosination is caused by hyperactivity of a microtubule-depolymerizing Kinesin-13 homolog, demonstrating its function as a key reader of the trypanosomatid-tubulin code. Taken together, our work establishes the importance of tubulin detyrosination in remodeling the microtubule-based cytoskeleton required for efficient proliferation in the mammalian host. This highlights tubulin detyrosination as a potential target for therapeutic action against leishmaniasis.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2415296122","type":"journal-article","created":{"date-parts":[[2025,1,14]],"date-time":"2025-01-14T13:37:30Z","timestamp":1736861850000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":14,"title":["Tubulin detyrosination shapes\n                    <i>Leishmania<\/i>\n                    cytoskeletal architecture and virulence"],"prefix":"10.1073","volume":"122","author":[{"given":"Rosa Milagros","family":"Corrales","sequence":"first","affiliation":[{"name":"Maladies infectieuses et Vecteurs: Ecologie, G\u00e9n\u00e9tique, Evolution et Contr\u00f4le, University of Montpellier, CNRS, Institut de Recherche pour le D\u00e9veloppement","place":["Montpellier, 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France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gr\u00e9goire","family":"Pasquier","sequence":"additional","affiliation":[{"name":"Maladies infectieuses et Vecteurs: Ecologie, G\u00e9n\u00e9tique, Evolution et Contr\u00f4le, University of Montpellier, CNRS, Institut de Recherche pour le D\u00e9veloppement","place":["Montpellier, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0584-1063","authenticated-orcid":false,"given":"Ghislain","family":"Gillard","sequence":"additional","affiliation":[{"name":"Tubulin Code team, Institute of Human Genetics, CNRS, Universit\u00e9 Montpellier","place":["Montpellier, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chantal","family":"Cazevieille","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Montpellier, INSERM U1298, Institute for Neurosciences of Montpellier","place":["Montpellier, 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