Cited by 218Toxoplasma gondii Research StudiesCoccidia and coccidiosis researchMalaria Research and Control

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A Novel Family of Toxoplasma IMC Proteins Displays a Hierarchical Organization and Functions in Coordinating Parasite Division

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Beck, Josh R., Rodriguez-Fernandez, Imilce A., Cruz de Leon, Jessica, Huynh, My-Hang, Carruthers, Vern B., Morrissette, Naomi S., Bradley, Peter J.·2010·PLoS Pathogens

DOI 10.1371/journal.ppat.1001094PMC PMC2936552

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Abstract

Apicomplexans employ a peripheral membrane system called the inner membrane complex (IMC) for critical processes such as host cell invasion and daughter cell formation. We have identified a family of proteins that define novel sub-compartments of the Toxoplasma gondii IMC. These IMC Sub-compartment Proteins, ISP1, 2 and 3, are conserved throughout the Apicomplexa, but do not appear to be present outside the phylum. ISP1 localizes to the apical cap portion of the IMC, while ISP2 localizes to a central IMC region and ISP3 localizes to a central plus basal region of the complex. Targeting of all three ISPs is dependent upon N-terminal residues predicted for coordinated myristoylation and palmitoylation. Surprisingly, we show that disruption of ISP1 results in a dramatic relocalization of ISP2 and ISP3 to the apical cap. Although the N-terminal region of ISP1 is necessary and sufficient for apical cap targeting, exclusion of other family members requires the remaining C-terminal region of the protein. This gate-keeping function of ISP1 reveals an unprecedented mechanism of interactive and hierarchical targeting of proteins to establish these unique sub-compartments in the Toxoplasma IMC. Finally, we show that loss of ISP2 results in severe defects in daughter cell formation during endodyogeny, indicating a role for the ISP proteins in coordinating this unique process of Toxoplasma replication.

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Authors: Beck, J. R., Rodriguez-Fernandez, I. A., Cruz de Leon, J., Huynh, M.-H., Carruthers, V. B., Morrissette, N. S., & Bradley, P. J.
Affiliations: University of California, Los Angeles (US)
University of Michigan (US)
University of California, Irvine (US)
Corresponding author: Bradley, Peter J.
ORCID: Beck, Josh R.
Carruthers, Vern B.
Morrissette, Naomi S.
Bradley, Peter J.
Venue: PLoS Pathogens
Publisher: Public Library of Science (PLoS)
Published: 2010-09-09
Volume: 6
Issue: 9
Pages: e1001094
ISSN: 1553-7366 (ISSN-L)
1553-7374
DOI: 10.1371/journal.ppat.1001094
PMC: PMC2936552
OpenAlex: W1996756350
Cited by: 217
References: 61
Citations by year: 2026: 4 · 2025: 17 · 2024: 15 · 2023: 13 · 2022: 10 · 2021: 22 · 2020: 15 · 2019: 20 · 2018: 8 · 2017: 14 · 2016: 17 · 2015: 15 · 2014: 12 · 2013: 12 · 2012: 13
FWCI: 8.62
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by
creativecommons.org/licenses/by/4.0/ (unspecified)
Locations: PLoS Pathogens (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
eScholarship (California Digital Library) (submittedVersion, cc-by)
Figshare (submittedVersion, cc-by)
Funders: National Institutes of Health (4r01ai064616-10, NIH-R01)
U.S. Public Health Service (R01 #A121423)
National Institute of Allergy and Infectious Diseases (R01 #AI064616, T32AI07323, R01AI067981, R01AI046675, T32AI007323)
Topics: Life Sciences › Immunology and Microbiology › Parasitology › Toxoplasma gondii Research Studies
Life Sciences › Agricultural and Biological Sciences › Animal Science and Zoology › Coccidia and coccidiosis research
Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Malaria Research and Control
Keywords: Toxoplasma gondii, inner membrane complex, apical cap, protein subcellular targeting, myristoylation, palmitoylation, endodyogeny, cell division, Apicomplexa, parasite replication
MeSH terms: Amino Acid Sequence, Animals, Cell Division, Cell Membrane, Cells, Cultured, Fibroblasts, Humans, Immunoglobulin G, Immunization, Male, Membrane Proteins, Mice, Inbred BALB C, Molecular Sequence Data, RNA, Messenger, Toxoplasma, Toxoplasmosis, Blotting, Western, Protozoan Proteins, Mutagenesis, Site-Directed, Sequence Homology, Amino Acid, Reverse Transcriptase Polymerase Chain Reaction, Mice, Foreskin

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A Novel Family of Toxoplasma IMC Proteins Displays a Hierarchical Organization and Functions in Coordinating Parasite Division

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