An Arginine Deprivation Response Pathway Is Induced in Leishmania during Macrophage Invasion

Goldman-Pinkovich, Adele; Balno, Caitlin; Strasser, Rona; Zeituni-Molad, Michal; Bendelak, Keren; Rentsch, Doris; Ephros, Moshe; Wiese, Martin; Jardim, Armando; Myler, Peter J.; Zilberstein, Dan (2016). An Arginine Deprivation Response Pathway Is Induced in Leishmania during Macrophage Invasion. PLoS pathogens, 12(4), e1005494. Public Library of Science 10.1371/journal.ppat.1005494

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

08 Faculty of Science > Department of Biology > Institute of Plant Sciences (IPS) > Molecular Plant Physiology
08 Faculty of Science > Department of Biology > Institute of Plant Sciences (IPS)

UniBE Contributor:

Rentsch, Doris

Subjects:

500 Science > 580 Plants (Botany)

ISSN:

1553-7366

Publisher:

Public Library of Science

Language:

English

Submitter:

Peter Alfred von Ballmoos-Haas

Date Deposited:

21 Jul 2016 11:21

Last Modified:

01 Feb 2017 12:52

Publisher DOI:

10.1371/journal.ppat.1005494

PubMed ID:

27043018

BORIS DOI:

10.7892/boris.84544

URI:

https://boris.unibe.ch/id/eprint/84544

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