A glycosylphosphatidylinositol-anchored carbonic anhydrase-related protein of Toxoplasma gondii is important for rhoptry biogenesis and virulence

Chasen, N. M., Asady, B., Lemgruber, L. , Vommaro, R. C., Kissinger, J. C., Coppens, I. and Moreno, S. N.J. (2017) A glycosylphosphatidylinositol-anchored carbonic anhydrase-related protein of Toxoplasma gondii is important for rhoptry biogenesis and virulence. mSphere, 2(3), e00027-17. (doi: 10.1128/mSphere.00027-17) (PMID:28529974) (PMCID:PMC5437132)

[img]
Preview
Text
140199.pdf - Published Version
Available under License Creative Commons Attribution.

4MB

Abstract

Carbonic anhydrase-related proteins (CARPs) have previously been described as catalytically inactive proteins closely related to α-carbonic anhydrases (α-CAs). These CARPs are found in animals (both vertebrates and invertebrates) and viruses as either independent proteins or domains of other proteins. We report here the identification of a new CARP (TgCA_RP) in the unicellular organism Toxoplasma gondii that is related to the recently described η-class CA found in Plasmodium falciparum. TgCA_RP is posttranslationally modified at its C terminus with a glycosylphosphatidylinositol anchor that is important for its localization in intracellular tachyzoites. The protein localizes throughout the rhoptry bulbs of mature tachyzoites and to the outer membrane of nascent rhoptries in dividing tachyzoites, as demonstrated by immunofluorescence and immunoelectron microscopy using specific antibodies. T. gondii mutant tachyzoites lacking TgCA_RP display a growth and invasion phenotype in vitro and have atypical rhoptry morphology. The mutants also exhibit reduced virulence in a mouse model. Our results show that TgCA_RP plays an important role in the biogenesis of rhoptries.

Item Type:Articles
Additional Information:Funding for this work was provided by the U.S. National Institutes of Health (grants AI-110027 and AI-096836 to SNJM, AI060767 to IC). NC was supported by a pre-doctoral fellowship from the American Heart Association (14PRE19100003). LL was supported by a postdoctoral fellowship from the Programa de Apoio ao Desenvolvimento da Metrologia, Qualidade e Tecnologia (PRONAMETRO) from the Instituto Nacional de Metrologia Qualidade e Tecnologia (INMETRO). RCV was supported by the Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ) and the Conselho Nacional de pesquisa (CNPq).
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Lemgruber Soares, Dr Leandro
Authors: Chasen, N. M., Asady, B., Lemgruber, L., Vommaro, R. C., Kissinger, J. C., Coppens, I., and Moreno, S. N.J.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:mSphere
Publisher:American Society for Microbiology
ISSN:2379-5042
ISSN (Online):2379-5042
Published Online:17 May 2017
Copyright Holders:Copyright © 2017 Chasen et al.
First Published:First published in mSphere 2(3): e00027-17
Publisher Policy:Reproduced under a Creative Commons License

University Staff: Request a correction | Enlighten Editors: Update this record