TY - DATA T1 - An Arginine Deprivation Response Pathway Is Induced in Leishmania during Macrophage Invasion PY - 2016/04/04 AU - Adele Goldman-Pinkovich AU - Caitlin Balno AU - Rona Strasser AU - Michal Zeituni-Molad AU - Keren Bendelak AU - Doris Rentsch AU - Moshe Ephros AU - Martin Wiese AU - Armando Jardim AU - Peter J. Myler AU - Dan Zilberstein UR - https://plos.figshare.com/articles/dataset/An_Arginine_Deprivation_Response_Pathway_Is_Induced_in_i_Leishmania_i_during_Macrophage_Invasion/3154435 DO - 10.1371/journal.ppat.1005494 L4 - https://ndownloader.figshare.com/files/4914307 L4 - https://ndownloader.figshare.com/files/4914310 KW - macrophage phagolysosomes KW - host defense response KW - analysis KW - lysosomal pools KW - Leishmania arginine transporter KW - Arginine Deprivation Response Pathway KW - macrophage arginine pool KW - Macrophage Invasion Amino acid KW - intracellular pools KW - extracellular levels KW - intracellular function KW - parasite monitors arginine levels KW - intracellular pathogen Leishmania N2 - 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. ER -