Absence of DEATH kinesin is fatal for Leishmania mexicana amastigotes

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Al Kufi, Suad Gazi Jaafer and Emmerson, Josiah and Rosenqvist, Heidi and Garcia, Catarina Mateus Moreira and Rios-Szwed, Diana Onodelia and Wiese, Martin (2022) Absence of DEATH kinesin is fatal for Leishmania mexicana amastigotes. Scientific Reports, 12 (1). 3266. ISSN 2045-2322 (https://doi.org/10.1038/s41598-022-07412-z)

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Abstract

Kinesins are motor proteins present in organisms from protists to mammals playing important roles in cell division, intracellular organisation and flagellum formation and maintenance. Leishmania mexicana is a protozoan parasite of the order Kinetoplastida causing human cutaneous leishmaniasis. Kinetoplastida genome sequence analyses revealed a large number of kinesins showing sequence and structure homology to eukaryotic kinesins. Here, we investigate the L. mexicana kinesin LmxKIN29 (LmxM.29.0350), also called DEATH kinesin. The activated MAP kinase LmxMPK3, a kinase affecting flagellum length in Leishmania, is able to phosphorylate recombinant full length LmxKIN29 at serine 554. Insect promastigote LmxKIN29 Leishmania null mutants showed no obvious phenotype. However, in mouse infection experiments, the null mutants were unable to cause the disease, whereas LmxKIN29 add-backs and single allele knockouts caused footpad lesions. Localisation using promastigotes expressing GFP-tagged LmxKIN29 revealed that the kinesin is predominantly found in between the nucleus and the flagellar pocket, while in dividing cells the GFP-fusion protein was found at the anterior and posterior ends of the cells indicating a role in cytokinesis. The inability to cause lesions in infected animals and the amino acid sequence divergence from mammalian kinesins suggests that LmxKIN29 is a potential drug target against leishmaniasis.

ORCID iDs

Al Kufi, Suad Gazi Jaafer ORCID logoORCID: https://orcid.org/0000-0003-4028-0214, Emmerson, Josiah, Rosenqvist, Heidi, Garcia, Catarina Mateus Moreira, Rios-Szwed, Diana Onodelia and Wiese, Martin ORCID logoORCID: https://orcid.org/0000-0003-4493-0835;
CORE (COnnecting REpositories)