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SPARK regulates AGC kinases central to the Toxoplasma gondii asexual cycle

Apicomplexan parasites balance proliferation, persistence, and spread in their metazoan hosts. AGC kinases, such as PKG, PKA, and the PDK1 ortholog SPARK, integrate environmental signals to toggle parasites between replicative and motile life stages. Recent studies have cataloged pathways downstream...

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Autores principales: Herneisen, Alice L., Peters, Michelle L., Smith, Tyler A., Lourido, Sebastian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10634940/
https://www.ncbi.nlm.nih.gov/pubmed/37961644
http://dx.doi.org/10.1101/2023.10.30.564746
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author Herneisen, Alice L.
Peters, Michelle L.
Smith, Tyler A.
Lourido, Sebastian
author_facet Herneisen, Alice L.
Peters, Michelle L.
Smith, Tyler A.
Lourido, Sebastian
author_sort Herneisen, Alice L.
collection PubMed
description Apicomplexan parasites balance proliferation, persistence, and spread in their metazoan hosts. AGC kinases, such as PKG, PKA, and the PDK1 ortholog SPARK, integrate environmental signals to toggle parasites between replicative and motile life stages. Recent studies have cataloged pathways downstream of apicomplexan PKG and PKA; however, less is known about the global integration of AGC kinase signaling cascades. Here, conditional genetics coupled to unbiased proteomics demonstrates that SPARK complexes with an elongin-like protein to regulate the stability of PKA and PKG in the model apicomplexan Toxoplasma gondii. Defects attributed to SPARK depletion develop after PKG and PKA are down-regulated. Parasites lacking SPARK differentiate into the chronic form of infection, which may arise from reduced activity of a coccidian-specific PKA ortholog. This work delineates the signaling topology of AGC kinases that together control transitions within the asexual cycle of this important family of parasites.
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spelling pubmed-106349402023-11-13 SPARK regulates AGC kinases central to the Toxoplasma gondii asexual cycle Herneisen, Alice L. Peters, Michelle L. Smith, Tyler A. Lourido, Sebastian bioRxiv Article Apicomplexan parasites balance proliferation, persistence, and spread in their metazoan hosts. AGC kinases, such as PKG, PKA, and the PDK1 ortholog SPARK, integrate environmental signals to toggle parasites between replicative and motile life stages. Recent studies have cataloged pathways downstream of apicomplexan PKG and PKA; however, less is known about the global integration of AGC kinase signaling cascades. Here, conditional genetics coupled to unbiased proteomics demonstrates that SPARK complexes with an elongin-like protein to regulate the stability of PKA and PKG in the model apicomplexan Toxoplasma gondii. Defects attributed to SPARK depletion develop after PKG and PKA are down-regulated. Parasites lacking SPARK differentiate into the chronic form of infection, which may arise from reduced activity of a coccidian-specific PKA ortholog. This work delineates the signaling topology of AGC kinases that together control transitions within the asexual cycle of this important family of parasites. Cold Spring Harbor Laboratory 2023-10-30 /pmc/articles/PMC10634940/ /pubmed/37961644 http://dx.doi.org/10.1101/2023.10.30.564746 Text en https://creativecommons.org/licenses/by/4.0/This work is licensed under a Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/) , which allows reusers to distribute, remix, adapt, and build upon the material in any medium or format, so long as attribution is given to the creator. The license allows for commercial use.
spellingShingle Article
Herneisen, Alice L.
Peters, Michelle L.
Smith, Tyler A.
Lourido, Sebastian
SPARK regulates AGC kinases central to the Toxoplasma gondii asexual cycle
title SPARK regulates AGC kinases central to the Toxoplasma gondii asexual cycle
title_full SPARK regulates AGC kinases central to the Toxoplasma gondii asexual cycle
title_fullStr SPARK regulates AGC kinases central to the Toxoplasma gondii asexual cycle
title_full_unstemmed SPARK regulates AGC kinases central to the Toxoplasma gondii asexual cycle
title_short SPARK regulates AGC kinases central to the Toxoplasma gondii asexual cycle
title_sort spark regulates agc kinases central to the toxoplasma gondii asexual cycle
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10634940/
https://www.ncbi.nlm.nih.gov/pubmed/37961644
http://dx.doi.org/10.1101/2023.10.30.564746
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