A Member of the Ferlin Calcium Sensor Family Is Essential for <named-content content-type="genus-species">Toxoplasma gondii</named-content> Rhoptry Secretion

ABSTRACT Invasion of host cells by apicomplexan parasites such as Toxoplasma gondii is critical for their infectivity and pathogenesis. In Toxoplasma, secretion of essential egress, motility, and invasion-related proteins from microneme organelles is regulated by oscillations of intracellular Ca2+....

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Autores principales:	Bradley I. Coleman, Sudeshna Saha, Seiko Sato, Klemens Engelberg, David J. P. Ferguson, Isabelle Coppens, Melissa B. Lodoen, Marc-Jan Gubbels
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2018
Materias:	Toxoplasma gondii calcium ferlin micronemes protein secretion rhoptries Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/02ef691e1abc4316a0c22d50ae4b1d0a
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spelling	oai:doaj.org-article:02ef691e1abc4316a0c22d50ae4b1d0a2021-11-15T15:58:20ZA Member of the Ferlin Calcium Sensor Family Is Essential for <named-content content-type="genus-species">Toxoplasma gondii</named-content> Rhoptry Secretion10.1128/mBio.01510-182150-7511https://doaj.org/article/02ef691e1abc4316a0c22d50ae4b1d0a2018-11-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01510-18https://doaj.org/toc/2150-7511ABSTRACT Invasion of host cells by apicomplexan parasites such as Toxoplasma gondii is critical for their infectivity and pathogenesis. In Toxoplasma, secretion of essential egress, motility, and invasion-related proteins from microneme organelles is regulated by oscillations of intracellular Ca2+. Later stages of invasion are considered Ca2+ independent, including the secretion of proteins required for host cell entry and remodeling from the parasite’s rhoptries. We identified a family of three Toxoplasma proteins with homology to the ferlin family of double C2 domain-containing Ca2+ sensors. In humans and model organisms, such Ca2+ sensors orchestrate Ca2+-dependent exocytic membrane fusion with the plasma membrane. Here we focus on one ferlin that is conserved across the Apicomplexa, T. gondii FER2 (TgFER2). Unexpectedly, conditionally TgFER2-depleted parasites secreted their micronemes normally and were completely motile. However, these parasites were unable to invade host cells and were therefore not viable. Knockdown of TgFER2 prevented rhoptry secretion, and these parasites failed to form the moving junction at the parasite-host interface necessary for host cell invasion. Collectively, these data demonstrate the requirement of TgFER2 for rhoptry secretion in Toxoplasma tachyzoites and suggest a possible Ca2+ dependence of rhoptry secretion. These findings provide the first mechanistic insights into this critical yet poorly understood aspect of apicomplexan host cell invasion. IMPORTANCE Apicomplexan protozoan parasites, such as those causing malaria and toxoplasmosis, must invade the cells of their hosts in order to establish a pathogenic infection. Timely release of proteins from a series of apical organelles is required for invasion. Neither the vesicular fusion events that underlie secretion nor the observed reliance of the various processes on changes in intracellular calcium concentrations is completely understood. We identified a group of three proteins with strong homology to the calcium-sensing ferlin family, which are known to be involved in protein secretion in other organisms. Surprisingly, decreasing the amounts of one of these proteins (TgFER2) did not have any effect on the typically calcium-dependent steps in invasion. Instead, TgFER2 was essential for the release of proteins from organelles called rhoptries. These data provide a tantalizing first look at the mechanisms controlling the very poorly understood process of rhoptry secretion, which is essential for the parasite’s infection cycle.Bradley I. ColemanSudeshna SahaSeiko SatoKlemens EngelbergDavid J. P. FergusonIsabelle CoppensMelissa B. LodoenMarc-Jan GubbelsAmerican Society for MicrobiologyarticleToxoplasma gondiicalciumferlinmicronemesprotein secretionrhoptriesMicrobiologyQR1-502ENmBio, Vol 9, Iss 5 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Toxoplasma gondii calcium ferlin micronemes protein secretion rhoptries Microbiology QR1-502
spellingShingle	Toxoplasma gondii calcium ferlin micronemes protein secretion rhoptries Microbiology QR1-502 Bradley I. Coleman Sudeshna Saha Seiko Sato Klemens Engelberg David J. P. Ferguson Isabelle Coppens Melissa B. Lodoen Marc-Jan Gubbels A Member of the Ferlin Calcium Sensor Family Is Essential for <named-content content-type="genus-species">Toxoplasma gondii</named-content> Rhoptry Secretion
description	ABSTRACT Invasion of host cells by apicomplexan parasites such as Toxoplasma gondii is critical for their infectivity and pathogenesis. In Toxoplasma, secretion of essential egress, motility, and invasion-related proteins from microneme organelles is regulated by oscillations of intracellular Ca2+. Later stages of invasion are considered Ca2+ independent, including the secretion of proteins required for host cell entry and remodeling from the parasite’s rhoptries. We identified a family of three Toxoplasma proteins with homology to the ferlin family of double C2 domain-containing Ca2+ sensors. In humans and model organisms, such Ca2+ sensors orchestrate Ca2+-dependent exocytic membrane fusion with the plasma membrane. Here we focus on one ferlin that is conserved across the Apicomplexa, T. gondii FER2 (TgFER2). Unexpectedly, conditionally TgFER2-depleted parasites secreted their micronemes normally and were completely motile. However, these parasites were unable to invade host cells and were therefore not viable. Knockdown of TgFER2 prevented rhoptry secretion, and these parasites failed to form the moving junction at the parasite-host interface necessary for host cell invasion. Collectively, these data demonstrate the requirement of TgFER2 for rhoptry secretion in Toxoplasma tachyzoites and suggest a possible Ca2+ dependence of rhoptry secretion. These findings provide the first mechanistic insights into this critical yet poorly understood aspect of apicomplexan host cell invasion. IMPORTANCE Apicomplexan protozoan parasites, such as those causing malaria and toxoplasmosis, must invade the cells of their hosts in order to establish a pathogenic infection. Timely release of proteins from a series of apical organelles is required for invasion. Neither the vesicular fusion events that underlie secretion nor the observed reliance of the various processes on changes in intracellular calcium concentrations is completely understood. We identified a group of three proteins with strong homology to the calcium-sensing ferlin family, which are known to be involved in protein secretion in other organisms. Surprisingly, decreasing the amounts of one of these proteins (TgFER2) did not have any effect on the typically calcium-dependent steps in invasion. Instead, TgFER2 was essential for the release of proteins from organelles called rhoptries. These data provide a tantalizing first look at the mechanisms controlling the very poorly understood process of rhoptry secretion, which is essential for the parasite’s infection cycle.
format	article
author	Bradley I. Coleman Sudeshna Saha Seiko Sato Klemens Engelberg David J. P. Ferguson Isabelle Coppens Melissa B. Lodoen Marc-Jan Gubbels
author_facet	Bradley I. Coleman Sudeshna Saha Seiko Sato Klemens Engelberg David J. P. Ferguson Isabelle Coppens Melissa B. Lodoen Marc-Jan Gubbels
author_sort	Bradley I. Coleman
title	A Member of the Ferlin Calcium Sensor Family Is Essential for <named-content content-type="genus-species">Toxoplasma gondii</named-content> Rhoptry Secretion
title_short	A Member of the Ferlin Calcium Sensor Family Is Essential for <named-content content-type="genus-species">Toxoplasma gondii</named-content> Rhoptry Secretion
title_full	A Member of the Ferlin Calcium Sensor Family Is Essential for <named-content content-type="genus-species">Toxoplasma gondii</named-content> Rhoptry Secretion
title_fullStr	A Member of the Ferlin Calcium Sensor Family Is Essential for <named-content content-type="genus-species">Toxoplasma gondii</named-content> Rhoptry Secretion
title_full_unstemmed	A Member of the Ferlin Calcium Sensor Family Is Essential for <named-content content-type="genus-species">Toxoplasma gondii</named-content> Rhoptry Secretion
title_sort	member of the ferlin calcium sensor family is essential for <named-content content-type="genus-species">toxoplasma gondii</named-content> rhoptry secretion
publisher	American Society for Microbiology
publishDate	2018
url	https://doaj.org/article/02ef691e1abc4316a0c22d50ae4b1d0a
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A Member of the Ferlin Calcium Sensor Family Is Essential for <named-content content-type="genus-species">Toxoplasma gondii</named-content> Rhoptry Secretion

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