Proteomics

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De novo mapping of the apicomplexan Ca2+-responsive phosphoproteome


ABSTRACT: Apicomplexan parasites cause persistent mortality and morbidity worldwide through diseases including malaria, toxoplasmosis, and cryptosporidiosis. Ca2+ signaling pathways have been repurposed in these eukaryotic pathogens to regulate parasite-specific cellular processes governing the transition between the replicative and lytic phases of the infectious cycle. Despite the presence of conserved Ca2+-responsive proteins, little is known about how specific signaling elements interact to impact pathogenesis. We mapped the Ca2+-responsive proteome of the model apicomplexan T. gondii via time-resolved phosphoproteomics. The waves of phosphoregulation following PKG activation and stimulated Ca2+ release corroborate known physiological changes but identify specific molecular targets in these pathways. We characterized protein phosphatase 1 (PP1) as a Ca2+-responsive enzyme that relocalized to the parasite apex upon Ca2+ store release. Conditional depletion of PP1 revealed that the phosphatase regulates Ca2+ uptake to promote parasite motility. PP1 may thus be partly responsible for Ca2+-regulated serine/threonine phosphatase activity in apicomplexan parasites.

INSTRUMENT(S): Orbitrap Exploris 480

ORGANISM(S): Toxoplasma Gondii Rh

SUBMITTER: Alice Herneisen  

LAB HEAD: Sebastian Lourido

PROVIDER: PXD033765 | Pride | 2022-10-15

REPOSITORIES: Pride

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Publications

Temporal and thermal profiling of the <i>Toxoplasma</i> proteome implicates parasite Protein Phosphatase 1 in the regulation of Ca<sup>2+</sup>-responsive pathways.

Herneisen Alice L AL   Li Zhu-Hong ZH   Chan Alex W AW   Moreno Silvia N J SNJ   Lourido Sebastian S  

eLife 20220817


Apicomplexan parasites cause persistent mortality and morbidity worldwide through diseases including malaria, toxoplasmosis, and cryptosporidiosis. Ca<sup>2+</sup> signaling pathways have been repurposed in these eukaryotic pathogens to regulate parasite-specific cellular processes governing the replicative and lytic phases of the infectious cycle, as well as the transition between them. Despite the presence of conserved Ca<sup>2+</sup>-responsive proteins, little is known about how specific sig  ...[more]

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