Absence of DEATH kinesin is fatal for Leishmania mexicana amastigotes

Suad Gazi Jaafer Al Kufi, Josiah Emmerson, Heidi Rosenqvist, Catarina Mateus Moreira Garcia, Diana Onodelia Rios-Szwed, Martin Wiese

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)
1 Downloads (Pure)

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.
Original languageEnglish
Article number3266
Number of pages13
JournalScientific Reports
Volume12
Issue number1
DOIs
Publication statusPublished - 28 Feb 2022

Keywords

  • absence
  • DEATH
  • kinesin
  • Leishmania mexicana
  • amastigotes

Fingerprint

Dive into the research topics of 'Absence of DEATH kinesin is fatal for Leishmania mexicana amastigotes'. Together they form a unique fingerprint.

Cite this