Phospho-relay feedback loops control egress vs. intracellular development in Toxoplasma gondii

被引:0
作者
Claywell, Ja E. [1 ]
Fu, Yong [1 ]
Sibley, L. David [1 ]
机构
[1] Washington Univ, Sch Med, Dept Mol Microbiol, 660 S Euclid Ave, St Louis, MO 63110 USA
来源
CELL REPORTS | 2025年 / 44卷 / 02期
关键词
DEPENDENT PROTEIN-KINASE; LYTIC CYCLE; CALCIUM; INVASION; DOMAINS; PHOSPHODIESTERASES; INHIBITORS; MOTILITY; IDENTIFICATION; SECRETION;
D O I
10.1016/j.celrep.2025.115260
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
The intracellular parasite Toxoplasma gondii alternates between a motile invasive and a quiescent intracellular replicative form, yet how these transitions are regulated is unknown. A positive feedback loop involving protein kinase G (PKG) and calcium-dependent PKs (CDPKs) controls motility, invasion, and egress by Toxoplasma gondii, while PKA isoform c1 (PKAc1) counteracts this pathway. Shortly after invasion, PKAc1 is activated by cyclic AMP (cAMP) produced by adenylate cyclases, leading to the suppression of the PKG/CDPK pathway. PKAc1 further activates phosphodiesterase 2, which selectively consumes cAMP, thus forming a negative feedback loop, causing transient activation of PKAc1. Perturbation of cyclic GMP (cGMP) vs. calcium demonstrates that PKAc1 acts on targets between guanylate cyclase and calcium release. The combined activation of PKG/CDPKs and inhibition by PKAc1, controlled by a transient negative feedback loop, ensures that the parasite is responsive to environmental signals needed to activate motility while also ensuring periods of long-term stable intracellular growth.
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页数:23
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共 59 条
[1]   Phosphoproteomics reveals malaria parasite Protein Kinase G as a signalling hub regulating egress and invasion [J].
Alam, Mahmood M. ;
Solyakov, Lev ;
Bottrill, Andrew R. ;
Flueck, Christian ;
Siddiqui, Faiza A. ;
Singh, Shailja ;
Mistry, Sharad ;
Viskaduraki, Maria ;
Lee, Kate ;
Hopp, Christine S. ;
Chitnis, Chetan E. ;
Doerig, Christian ;
Moon, Robert W. ;
Green, Judith L. ;
Holder, Anthony A. ;
Baker, David A. ;
Tobin, Andrew B. .
NATURE COMMUNICATIONS, 2015, 6
[2]   A time- and cost-efficient system for high-level protein production in mammalian cells [J].
Aricescu, A. Radu ;
Lu, Weixian ;
Jones, E. Yvonne .
ACTA CRYSTALLOGRAPHICA SECTION D-STRUCTURAL BIOLOGY, 2006, 62 :1243-1250
[3]   A novel epitope tag system to study protein targeting and organelle biogenesis in Trypanosoma brucei [J].
Bastin, P ;
Bagherzadeh, A ;
Matthews, KR ;
Gull, K .
MOLECULAR AND BIOCHEMICAL PARASITOLOGY, 1996, 77 (02) :235-239
[4]   Toxoplasma gondii merozoite gene expression analysis with comparison to the life cycle discloses a unique expression state during enteric development [J].
Behnke, Michael S. ;
Zhang, Tiange P. ;
Dubey, Jitender P. ;
Sibley, L. David .
BMC GENOMICS, 2014, 15
[5]   Calcium-Dependent Signaling and Kinases in Apicomplexan Parasites [J].
Billker, Oliver ;
Lourido, Sebastian ;
Sibley, L. David .
CELL HOST & MICROBE, 2009, 5 (06) :612-622
[6]   Phosphatidic acid governs natural egress in Toxoplasma gondii via a guanylate cyclase receptor platform [J].
Bisio, Hugo ;
Lunghi, Matteo ;
Brochet, Mathieu ;
Soldati-Favre, Dominique .
NATURE MICROBIOLOGY, 2019, 4 (03) :420-428
[7]   Lytic Cycle of Toxoplasma gondii: 15 Years Later [J].
Blader, Ira J. ;
Coleman, Bradley I. ;
Chen, Chun-Ti ;
Gubbels, Marc-Jan .
ANNUAL REVIEW OF MICROBIOLOGY, VOL 69, 2015, 69 :463-485
[8]   Calcium Signaling throughout the Toxoplasma gondii Lytic Cycle A STUDY USING GENETICALLY ENCODED CALCIUM INDICATORS [J].
Borges-Pereira, Lucas ;
Budu, Alexandre ;
McKnight, Ciara A. ;
Moore, Christina A. ;
Vella, Stephen A. ;
Triana, Miryam A. Hortua ;
Liu, Jing ;
Garcia, Celia R. S. ;
Pace, Douglas A. ;
Moreno, Silvia N. J. .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2015, 290 (45) :26914-26926
[9]   Feedback loops shape cellular signals in space and time [J].
Brandman, Onn ;
Meyer, Tobias .
SCIENCE, 2008, 322 (5900) :390-395
[10]   Essential cGMP Signaling in Toxoplasma Is Initiated by a Hybrid P-Type ATPase-Guanylate Cyclase [J].
Brown, Kevin M. ;
Sibley, L. David .
CELL HOST & MICROBE, 2018, 24 (06) :804-+