An Arginine Deprivation Response Pathway Is Induced in Leishmania during Macrophage Invasion.
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 Leishma...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2016-04-01
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| Series: | PLoS Pathogens |
| Online Access: | http://europepmc.org/articles/PMC4846328?pdf=render |
| _version_ | 1811275978741121024 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Adele Goldman-Pinkovich |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-12T23:48:17Z |
| format | Article |
| id | doaj.art-92d09b6bcaf5498d946c3f926d9421cc |
| institution | Directory Open Access Journal |
| issn | 1553-7366 1553-7374 |
| language | English |
| last_indexed | 2024-04-12T23:48:17Z |
| publishDate | 2016-04-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj.art-92d09b6bcaf5498d946c3f926d9421cc2022-12-22T03:11:48ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742016-04-01124e100549410.1371/journal.ppat.1005494An Arginine Deprivation Response Pathway Is Induced in Leishmania during Macrophage Invasion.Adele Goldman-PinkovichCaitlin BalnoRona StrasserMichal Zeituni-MoladKeren BendelakDoris RentschMoshe EphrosMartin WieseArmando JardimPeter J MylerDan ZilbersteinAmino 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.http://europepmc.org/articles/PMC4846328?pdf=render |
| spellingShingle | 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 An Arginine Deprivation Response Pathway Is Induced in Leishmania during Macrophage Invasion. PLoS Pathogens |
| title | An Arginine Deprivation Response Pathway Is Induced in Leishmania during Macrophage Invasion. |
| title_full | An Arginine Deprivation Response Pathway Is Induced in Leishmania during Macrophage Invasion. |
| title_fullStr | An Arginine Deprivation Response Pathway Is Induced in Leishmania during Macrophage Invasion. |
| title_full_unstemmed | An Arginine Deprivation Response Pathway Is Induced in Leishmania during Macrophage Invasion. |
| title_short | An Arginine Deprivation Response Pathway Is Induced in Leishmania during Macrophage Invasion. |
| title_sort | arginine deprivation response pathway is induced in leishmania during macrophage invasion |
| url | http://europepmc.org/articles/PMC4846328?pdf=render |
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