PXD064373

PXD064373 is an original dataset announced via ProteomeXchange.

Title	AP2-HS and a GDV1 regulatory feedback loop mediate environmental induction of sexual conversion in Plasmodium falciparum
Description	Transmission of Plasmodium spp. from a human host to a mosquito vector requires that some parasites abandon the asexual replicative cycle in the blood, associated with all clinical symptoms of malaria, and convert into non-replicative sexual precursors called gametocytes. The sexual conversion rate (i.e., the proportion of parasites that convert at each cycle) is variable, which enables parasites to adjust the balance between sexual and asexual development to the conditions of the human blood environment. Under some specific types of stress, parasites enhance sexual conversion rates to increase their relative investment in transmission. Sexual conversion is orchestrated by the master regulator AP2-G, a transcription factor of the ApiAP2 family. In Plasmodium falciparum, the species that produces the vast majority of human malaria cases and deaths, activation of ap2-g expression requires the GDV1 protein, which displaces heterochromatin from the ap2-g promoter. An antisense long noncoding RNA (lncRNA) encoded in the same locus as GDV1, named gdv1-as, is a negative regulator of GDV1 expression, but how the expression of this lncRNA is regulated or how specific types of stress enhance sexual conversion is not known. Here we show that environmental induction of sexual conversion is initiated by activation of gdv1 expression in a process dependent on the AP2-HS transcription factor, previously described as the activator of the malarial protective HS response. Next, GDV1 activates the expression of its own repressor, gdv1-as, by removing heterochromatin from its putative promoter. This positive-negative regulatory feedback loop limits GDV1 activation to a short burst of expression. This same mechanism operates for stimulation of sexual conversion by different environmental conditions, and AP2-HS is also needed for the activation of metabolic pathways that compensate depletion of phospholipid precursors. These findings provide new insight on the mechanisms underlying the fundamental developmental decision of malaria parasites and explain their plasticity to increase the investment in transmission when the conditions of the environment are unfavourable.
HostingRepository	PRIDE
AnnounceDate	2026-07-31
AnnouncementXML	Submission_2026-07-31_03:54:26.238.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Elisabet Tintó-Font
SpeciesList	scientific name: Plasmodium falciparum; NCBI TaxID: NEWT:5833;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Eclipse

Revision	Datetime	Status	ChangeLog Entry
0	2025-05-28 06:21:15	ID requested
1	2026-07-27 22:32:32	announced
⏵ 2	2026-07-31 03:54:26	announced	2026-07-31: Updated project metadata.

Dataset with its publication pending

submitter keyword: Plasmodium falciparum, DHA, sexual conversion, choline-depletion

Alfred Cortés
contact affiliation	Malaria Epigenetics Group Barcelona Institute for Global Health (ISGlobal) Barcelona, Spain
contact email	alfred.cortes@isglobal.org
lab head
Elisabet Tintó-Font
contact affiliation	ISGlobal
contact email	elisabet.tinto@isglobal.org
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/2026/07/PXD064373

PRIDE project URI

• PRIDE
  1. PXD064373
     1. Label: PRIDE project
     2. Name: AP2-HS and a GDV1 regulatory feedback loop mediate environmental induction of sexual conversion in Plasmodium falciparum