PXD020381-2

PXD020381 is an original dataset announced via ProteomeXchange.

Title	A multipass membrane protein interacts with the cGMP-dependent protein kinase to regulate critical calcium signals in malaria parasites
Description	In malaria parasites, all cGMP-dependent signalling is mediated through a single cGMP-dependent protein kinase (PKG). A major function of PKG is to control calcium signals essential for the parasite to exit red blood cells or for transmission to the mosquito vector. However, how PKG controls these signals in the absence of known second messenger-dependent calcium channels or scaffolding proteins remains a mystery. Here we identify a tightly-associated PKG partner protein in both Plasmodium falciparum asexual blood stages and P. berghei gametocytes. Named ICM1, the partner is a polytopic membrane protein with homology to transporters and calcium channels, raising the possibility of a direct functional link between PKG and calcium homeostasis. Phosphoproteomic analyses in both Plasmodium species highlight a densely phosphorylated region of ICM1 with multiple phosphorylation events dependent upon PKG activity. Stage-specific depletion of ICM1 in P. berghei blocks gametogenesis due to the inability of mutant parasites to mobilise intracellular calcium upon PKG activation, whilst conditional disruption of P. falciparum ICM1 results in reduced cGMP-dependent calcium mobilisation associated with defective egress and invasion. Our findings provide new insights into the atypical calcium homeostasis in malaria parasites essential for pathology and disease transmission.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_05:18:52.198.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Helen Flynn
SpeciesList	scientific name: Plasmodium falciparum (isolate 3D7); NCBI TaxID: 36329;
ModificationList	(R)-5-oxo-1; phosphorylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2020-07-15 07:17:48	ID requested
1	2021-10-11 10:47:48	announced
⏵ 2	2024-10-22 05:18:52	announced	2024-10-22: Updated project metadata.

Dataset with its publication pending

submitter keyword: transporter,plasmodium falciparum, calcium regulation, plasmodium berghei, phosphoproteomics, cGMP-dependent protein kinase (PKG)

Bram Snijders
contact affiliation	The Francis Crick Institute 1 Midland Road London NW1 1AT UK
contact email	bram.snijders@crick.ac.uk
lab head
Helen Flynn
contact affiliation	The Francis Crick Institute
contact email	helen.flynn@crick.ac.uk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD020381
     1. Label: PRIDE project
     2. Name: A multipass membrane protein interacts with the cGMP-dependent protein kinase to regulate critical calcium signals in malaria parasites