An arginine deprivation response pathway is induced in Leishmania during macrophage invasion
Goldman-Pinkovich, Adele and Balno, Caitlin and Strasser, Rona and Zeituni-Molad, Michal and Bendelak, Keren and Rentsch, Doris and Ephros, Moshe and Wiese, Martin and Jardim, Armando and Myler, Peter J and Zilberstein, Dan (2016) An arginine deprivation response pathway is induced in Leishmania during macrophage invasion. PLOS Pathogens, 12 (4). e1005494. ISSN 1553-7366 (https://doi.org/10.1371/journal.ppat.1005494)
Preview |
Other.
Filename: Goldman_Pinkovich_PP2016_an_arginine_deprivation_response_pathway_is_induced_in_leishmania.PDF
Final Published Version License: Download (2MB)| Preview |
Abstract
Amino acid sensing is an intracellular function that supports nutrient homeostasis, largely through controlled release of amino acids from lysosomal pools. The intracellular pathogen Leishmania resides and proliferates within human macrophage phagolysosomes. Here we describe a new pathway in Leishmania that specifically senses the extracellular levels of arginine, an amino acid that is essential for the parasite. During infection, the macrophage arginine pool is depleted due to its use to produce metabolites (NO and polyamines) that constitute part of the host defense response and its suppression, respectively. We found that parasites respond to this shortage of arginine by up-regulating expression and activity of the Leishmania arginine transporter (LdAAP3), as well as several other transporters. Our analysis indicates the parasite monitors arginine levels in the environment rather than the intracellular pools. Phosphoproteomics and genetic analysis indicates that the arginine-deprivation response is mediated through a mitogen-activated protein kinase-2-dependent signaling cascade.
ORCID iDs
Goldman-Pinkovich, Adele, Balno, Caitlin, Strasser, Rona, Zeituni-Molad, Michal, Bendelak, Keren, Rentsch, Doris, Ephros, Moshe, Wiese, Martin ORCID: https://orcid.org/0000-0003-4493-0835, Jardim, Armando, Myler, Peter J and Zilberstein, Dan;-
-
Item type: Article ID code: 56181 Dates: DateEvent4 April 2016Published16 February 2016AcceptedSubjects: Science > Natural history > Biology Department: Faculty of Science > Strathclyde Institute of Pharmacy and Biomedical Sciences Depositing user: Pure Administrator Date deposited: 18 Apr 2016 09:21 Last modified: 21 Oct 2024 00:21 URI: https://strathprints.strath.ac.uk/id/eprint/56181