PXD015093

PXD015093 is an original dataset announced via ProteomeXchange.

Title	Phosphorylation Dependent Assembly of a 14-3-3 Anchored Signaling Complex During Erythrocyte Invasion by Plasmodium falciparum Merozoites
Description	Red blood cell (RBC) invasion by Plasmodium merozoites requires multiple steps that are regulated by signalling pathways. However, the signalling pathways in merozoites that regulate microneme secretion and RBC invasion are not completely understood. Exposure of P. falciparum merozoites to a low potassium (K+) ionic environment as found in blood plasma has been shown to lead to a rise in cytosolic calcium (Ca2+), which triggers microneme secretion. Here, we present a phosphoproteome analysis of extracellular merozoites revealing 3700 phosphorylation sites of which 1705 were not previously known. Upon investigation of phosphorylation changes in merozoites subjected to different ionic environments (high K+/ low K+) we identified 394 protein phosphorylation sites out of which changes in 143 were Ca2+-dependent. We observed that the catalytic and regulatory subunits of protein kinase A (PfPKAc and PfPKAr), calcium-dependent protein kinase 1 (PfCDPK1) and scaffold protein Pf14-3-3I form a phosphorylation-dependent multiprotein complex when merozoites are exposed to the low K+ signal. Moreover, disruption of this complex using phospho-peptides, or small molecule inhibitors blocks microneme secretion and RBC invasion. This study sheds light on the regulatory mechanisms used by merozoites to invade RBCs and identifies new targets for development of drugs against malaria.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_05:19:43.969.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Thibaut Douché
SpeciesList	scientific name: Plasmodium falciparum (isolate 3D7); NCBI TaxID: 36329;
ModificationList	phosphorylated residue; monohydroxylated residue; acetylated residue; iodoacetamide derivatized residue
Instrument	LTQ Orbitrap Velos

Revision	Datetime	Status	ChangeLog Entry
0	2019-08-20 08:47:48	ID requested
1	2021-03-05 02:25:32	announced
⏵ 2	2024-10-22 05:19:49	announced	2024-10-22: Updated project metadata.

10.1128/mbio.01287-20;

More KR, Kaur I, Giai Gianetto Q, Invergo BM, Chaze T, Jain R, Huon C, Gutenbrunner P, Weisser H, Matondo M, Choudhary JS, Langsley G, Singh S, Chitnis CE, Phosphorylation-Dependent Assembly of a 14-3-3 Mediated Signaling Complex during Red Blood Cell Invasion by Plasmodium falciparum Merozoites. mBio, 11(4):(2020) [pubmed]

submitter keyword: LC MS-MS,Malaria, RBC invasion

Chetan Chitnis
contact affiliation	Malaria Parasite Biology and Vaccines, Department of Parasites and Insect Vectors, Institute Pastuer, 25-28 Rue du Docteur Roux 75015, Paris France
contact email	chetan.chitnis@pasteur.fr
lab head
Thibaut Douché
contact affiliation	Institut Pasteur
contact email	thibaut.douche@pasteur.fr
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2021/03/PXD015093

PRIDE project URI

• PRIDE
  1. PXD015093
     1. Label: PRIDE project
     2. Name: Phosphorylation Dependent Assembly of a 14-3-3 Anchored Signaling Complex During Erythrocyte Invasion by Plasmodium falciparum Merozoites