Overexpression of Leishmania major protein arginine methyltransferase 6 reduces parasite infectivity in vivo

Author(s)

Campagnaro, Gustavo Daniel ; Lorenzon, Lucas Bigolin ; Rodrigues, Mateus Augusto ; Defina, Tania Paula Aquino ; Pinzan, Camila Figueiredo ; Ferreira, Tiago Rodrigues ; Cruz, Angela Kaysel

• Document type: Journal article
• Source: Acta Tropica; v. 244, p. 7-pg., 2023-06-01.

Abstract

Arginine methylation is catalysed by Protein Arginine Methyltransferases (PRMTs) and can affect how a target protein functions and how it interacts with other macromolecules, which in turn impacts on cell metabolism and gene expression control. Leishmania parasites express five different PRMTs, and although the presence of each individual PRMT is not essential per se, the imbalanced activity of these PRMTs can impact the virulence of Leishmania parasites in vitro and in vivo. Here we created a Leishmania major cell line overexpressing PRMT6 and show that similar to what was observed for the T. brucei homologous enzyme, L. major PRMT6 probably has a narrow substrate range. However, its overexpression notably impairs the infection in mice, with a mild reduction in the number of viable parasites in the lymph nodes. Our results indicate that arginine methylation by LmjPRMT6 plays a significant role in the adaptation of the parasite to the environment found in the mammalian host. (AU)

• FAPESP's process: 15/13618-8 - Regulating the trans-regulators: investigating the PRMT7 molecular pathway as an epigenetic regulator of Leishmania virulence
• Grantee: Angela Kaysel Cruz
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 14/00220-3 - Effects of PRMT6 overexpression in the virulence levels of Leishmania
• Grantee: Mateus Augusto Rodrigues
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• FAPESP's process: 18/14398-0 - UK:Brazil Joint Centre Partnership in Leishmaniasis (JCPiL)
• Grantee: Angela Kaysel Cruz
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 13/13237-9 - Functional evaluation of the Leishmania major arginine methyltransferase LmjPRMT6.
• Grantee: Lucas Bigolin Lorenzon
• Support Opportunities: Scholarships in Brazil - Master
• FAPESP's process: 20/02372-6 - Actions coordinated by the enzyme Arginine Methyltransferase 5 of Leishmania braziliensis
• Grantee: Gustavo Daniel Campagnaro
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 10/01129-9 - Investigation of the function of the arginine methyltransferase LmjPRMT7 on the control of gene expression in Leishmania major
• Grantee: Tiago Rodrigues Ferreira
• Support Opportunities: Scholarships in Brazil - Doctorate