10.1371/journal.ppat.1005494 Adele Goldman-Pinkovich Adele Goldman-Pinkovich Caitlin Balno Caitlin Balno Rona Strasser Rona Strasser Michal Zeituni-Molad Michal Zeituni-Molad Keren Bendelak Keren Bendelak Doris Rentsch Doris Rentsch Moshe Ephros Moshe Ephros Martin Wiese Martin Wiese Armando Jardim Armando Jardim Peter J. Myler Peter J. Myler Dan Zilberstein Dan Zilberstein An Arginine Deprivation Response Pathway Is Induced in <i>Leishmania</i> during Macrophage Invasion Public Library of Science 2016 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 2016-04-04 12:46:20 Dataset 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>