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An Arginine Deprivation Response Pathway Is Induced in Leishmania during Macrophage Invasion
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نویسنده
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goldman-pinkovich a. ,balno c. ,strasser r. ,zeituni-molad m. ,bendelak k. ,rentsch d. ,ephros m. ,wiese m. ,jardim a. ,myler p.j. ,zilberstein d.
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منبع
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plos pathogens - 2016 - دوره : 12 - شماره : 4
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چکیده
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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. © 2016 goldman-pinkovich et al.
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آدرس
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faculty of biology,technion—israel institute of technology,haifa,haifa, Israel, faculty of biology,technion—israel institute of technology,haifa,haifa, Israel, institute of parasitology,mcgill university,ste anne de bellevue,qc,canada,department of biology,cégep john abbott college,sainte-anne-de-bellevue,qc, Canada, carmel medical center and faculty of medicine,technion,—israel institute of technology,haifa, Israel, the smoler proteomic center,faculty of biology,technion-israel institute of technology,haifa, Israel, institute of plant sciences,university of bern,bern, Switzerland, carmel medical center and faculty of medicine,technion,—israel institute of technology,haifa, Israel, strathclyde institute of pharmacy and biomedical sciences,university of strathclyde,glasgow, United Kingdom, institute of parasitology,mcgill university,ste anne de bellevue,qc, Canada, center for infectious disease research,formerly seattle biomedical research institute,seattle,wa,united states,departments of global health and biomedical informatics & medical education,university of washington,seattle wa, United States, faculty of biology,technion—israel institute of technology,haifa,haifa, Israel
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Authors
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