PXD005884

PXD005884 is an original dataset announced via ProteomeXchange.

Title	CDPK4 is a pleiotropic regulator controlling the atypical Plasmodium cell cycle during mosquito transmission
Description	Transmission of malaria parasites from humans to the mosquito vector exclusively relies on the sexual reproduction of the parasite within the mosquito blood meal. Upon ingestion, Plasmodium male gametocyte undergoes explosive development: within 10 minutes, it completes three rounds of genome replication and endomitosis, assembles eight axonemes, and emerges from the host red blood cell. The plant-like calcium-dependent protein kinase 4 (CDPK4) was previously shown to be essential for male gametogenesis placing this kinase as an attractive drug target to block malaria transmission. Here we have identified and resolved three distinct molecular functions of CDPK4 during male gametogenesis. Activity of a myristoylated isoform is first required up to 20 seconds after activation to load the Mini-Chromosome Maintenance complex onto origins of replication. This role is partially mediated by a conserved protein belonging to the SAPS-domain family which is involved in the G1 to S-phase transition in eukaryotes. At the same time, activity of myristoylated CDPK4 is required to phosphorylate a Plasmodium-specific microtubule-associated protein necessary for mitotic spindle assembly. Finally, activity of a short non-myristoylated isoform of CDPK4 is essential seconds prior to completion of cytokinesis and the activation of male gamete motility. This late role has been linked to another Plasmodium-specific protein that is incorporated into axonemes during gametogenesis. This study reveals how a kinase of a protist parasite integrates and transduces multiple signals with a high spatiotemporal resolution to control both evolutionarily conserved and Plasmodium-specific biological processes.
HostingRepository	PRIDE
AnnounceDate	2017-05-24
AnnouncementXML	Submission_2017-05-24_06:40:41.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	James Wright
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; scientific name: Plasmodium berghei; NCBI TaxID: 5821;
ModificationList	monoiodated tyrosine; 2-pyrrolidone-5-carboxylic acid (Gln); phosphorylated residue; monohydroxylated residue; acetylated residue; formylated residue; deamidated residue; iodoacetamide derivatized residue
Instrument	LTQ Orbitrap Velos; Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2017-02-08 07:32:33	ID requested
⏵ 1	2017-05-24 06:40:41	announced

Dataset with its publication pending

curator keyword: Biological, Biomedical

submitter keyword: LC-MSMS, affinity purification, phospho, thiophospho, malaria

Jyoti Choudhary
contact affiliation	Wellcome Trust Sanger Institute
contact email	jc4@sanger.ac.uk
lab head
James Wright
contact affiliation	Proteomic Mass Spectrometry, Wellcome Trust Sanger Institute
contact email	jw13@sanger.ac.uk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD005884
     1. Label: PRIDE project
     2. Name: CDPK4 is a pleiotropic regulator controlling the atypical Plasmodium cell cycle during mosquito transmission