An Arginine Deprivation Response Pathway Is Induced in <i>Leishmania</i> during Macrophage Invasion
Adele Goldman-Pinkovich
Caitlin Balno
Rona Strasser
Michal Zeituni-Molad
Keren Bendelak
Doris Rentsch
Moshe Ephros
Martin Wiese
Armando Jardim
Peter J. Myler
Dan Zilberstein
10.1371/journal.ppat.1005494
https://plos.figshare.com/articles/dataset/An_Arginine_Deprivation_Response_Pathway_Is_Induced_in_i_Leishmania_i_during_Macrophage_Invasion/3154435
<div><p>Amino acid sensing is an intracellular function that supports nutrient homeostasis, largely through controlled release of amino acids from lysosomal pools. The intracellular pathogen <i>Leishmania</i> resides and proliferates within human macrophage phagolysosomes. Here we describe a new pathway in <i>Leishmania</i> 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 <i>Leishmania</i> 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.</p></div>
2016-04-04 12:46:20
macrophage phagolysosomes
host defense response
analysis
lysosomal pools
Leishmania arginine transporter
Arginine Deprivation Response Pathway
macrophage arginine pool
Macrophage Invasion Amino acid
intracellular pools
extracellular levels
intracellular function
parasite monitors arginine levels
intracellular pathogen Leishmania