PXD002830

PXD002830 is an original dataset announced via ProteomeXchange.

Title	Arginine sensing in Leishmania
Description	Abstract Protozoa of the genus Leishmania are the causative agents of leishmaniasis in humans. These parasites cycle between promastigotes in the sand fly mid-gut and amastigotes in phagolysosome of mammalian macrophages. During infection, they up-regulate host nitric oxide synthase and arginase expression, both of which use arginine as a substrate. These elevated activities deplete macrophage arginine pools, a situation that invading Leishmania must overcome since it is an essential amino acid. Leishmania donovani imports exogenous arginine via a mono-specific amino acid transporter (AAP3) and utilizes it primarily through the polyamine pathway to provide precursors for trypanothione biosynthesis. Here we report the discovery of a pathway whereby promastigote and amastigote forms of the Leishmania sense the lack of environmental arginine and respond with rapid up-regulation in AAP3 expression and activity, as well as several other transporters. Significantly, this arginine deprivation response is also activated in parasites during macrophage infection. Phosphoproteomic analyses of L. donovani promastigotes have implicated a mitogen activated protein kinase 2 (MPK2)-mediated signaling cascade in this response and L. mexicana mutants lacking MPK2 are unable to respond to arginine deprivation. In addition, these mutants cannot differentiate into amastigotes in axenic culture or in peritoneal macrophages, and fail to establish an infection in mice. We propose that sensing arginine levels plays a critical role in Leishmania virulence by activating a rapid metabolic reaction for salvaging this amino acid in response to the lower arginine concentration in the macrophage phagolysosome.
HostingRepository	PRIDE
AnnounceDate	2016-04-11
AnnouncementXML	Submission_2016-04-11_01:37:35.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Keren Bendalak
SpeciesList	scientific name: Leishmania donovani; NCBI TaxID: 5661;
ModificationList	phosphorylated residue
Instrument	LTQ Orbitrap

Revision	Datetime	Status	ChangeLog Entry
0	2015-09-01 02:00:20	ID requested
⏵ 1	2016-04-11 01:37:36	announced

Goldman-Pinkovich A, Balno C, Strasser R, Zeituni-Molad M, Bendelak K, Rentsch D, Ephros M, Wiese M, Jardim A, Myler PJ, Zilberstein D, An Arginine Deprivation Response Pathway Is Induced in Leishmania during Macrophage Invasion. PLoS Pathog, 12(4):e1005494(2016) [pubmed]

curator keyword: Biomedical

submitter keyword: Leishmania, phosphoproteome, arginine sensing

Dan Zilberstein
contact affiliation	Faculty of Biology, Technion
contact email	danz@bi.technion.ac.il
lab head
Keren Bendalak
contact affiliation	Technion
contact email	kerenb@tx.technion.ac.il
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD002830
     1. Label: PRIDE project
     2. Name: Arginine sensing in Leishmania