Tubulin detyrosination shapes Leishmania cytoskeletal architecture and virulence

• DOI: 10.1073/pnas.2415296122
• Publication Date: 2025-01-14T18:37:30Z
• Authors: Rosa Milagros Cor...; Jeremy Vincent; Lucien Crobu; Rachel Neish; Binita Nepal; Julien Espeut; Grégoire Pasquier; Ghislain Gillard; Chantal Cazevieille; Jeremy C. Mottram; Dawn M. Wetzel; Yvon Sterkers; Krzysztof Rogowski; Maude F. Lévêque
• Keywords: Amastigote

Tubulin detyrosination has been implicated in various human disorders and is important for regulating microtubule dynamics. While most organisms this modification restricted to α-tubulin, trypanosomatid parasites, it occurs on both α- β-tubulin. Here, we show that Leishmania , a single vasohibin (LmVASH) enzyme responsible differential kinetics of β-tubulin detyrosination. LmVASH knockout which are completely devoid detyrosination, decreased levels glutamylation exhibit strongly diminished pathogenicity mice, correlating with proliferation macrophages. Reduced virulence associated altered morphogenesis flagellum remodeling detyrosination-deficient amastigotes. Flagellum shortening the absence caused by hyperactivity microtubule-depolymerizing Kinesin-13 homolog, demonstrating its function as key reader trypanosomatid-tubulin code. Taken together, our work establishes importance tubulin microtubule-based cytoskeleton required efficient mammalian host. This highlights potential target therapeutic action against leishmaniasis.