PXD025222

PXD025222 is an original dataset announced via ProteomeXchange.

Title	A divergent protein kinase A in the human pathogen Leishmania is associated with developmental morphogenesi
Description	Parasitic protozoa of the genus Leishmania are obligatory intracellular parasites that caus e human leishmaniasis . During their life, they cycle between the phagolysosome of mammalian macrophages ( round intracellular amastigotes ) , and the mid - gut of female sand flies ( elongated extracellular promastigotes ) . Shifting axenic promastigotes to a lysosome - like environment ( pH 5.5 and 37 ̊C , 5% C O 2 ) initiate s their development into amastigotes. Previous studies suggested a role for protein kinase A in differentiation initiation . In this study we assessed this hypothesis by describ ing a new , divergent , regulatory subunit of protein kinase A (LdPKAR3) whose phosphorylation is regulated by the differentiation signal . This protein exists exclusively in the genome s of Leishmania and T rypano soma cruzi , both obligatory intracellular parasites . W hile the C - terminal half of this protein is conserved , the N - termin al region is divergent and much longer than the consensus R subunits . We found that LdPKAR3 is bound to the subpellicular microtubules cell cortex via a formin FH2 domain at its N - terminal tip. Immunoprecipitation , fluorescence resonance energy transfer ( FRET ) , proteomics, and 3D modeling analyses indicated that LdPKAR3 associate s with the PKA catalytic subunit 3 (C3) to form a PKA holoenzyme , indicating that R3 is a true PKA regulatory subunit. In promastigotes, LdPKA R3 recruits C3 to the central region of the subpellicular microtubules , where it determines the ir elongated shape . Deleti ng either R3 or C3 resulted in significant rounding of most of the promastigote population . Adding back the full - length wild type genes restored the elongat e shape of promastigotes. This is the first time that a PKA regulatory s ubunit has been shown to play a role in Leishmania morphogenesis
HostingRepository	PRIDE
AnnounceDate	2024-03-21
AnnouncementXML	Submission_2024-03-21_06:11:03.047.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	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2021-04-06 07:14:26	ID requested
⏵ 1	2024-03-21 06:11:03	announced

Dataset with its publication pending

submitter keyword: Leishmania

differentiation

signal transduction

morphogenesis

parasites

Dan Zilberstein
contact affiliation	Faculty of Biology, Technion - Israel Institute of Technology, Haifa 32000, Haifa, Israel
contact email	danz@technion.ac.il
lab head
Keren Bendalak
contact affiliation	Technion
contact email	kerenb@technion.ac.il
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD025222
     1. Label: PRIDE project
     2. Name: A divergent protein kinase A in the human pathogen Leishmania is associated with developmental morphogenesi