A seven-helix protein constitutes stress granules crucial for regulating translation during human-to-mosquito transmission of Plasmodium falciparum

Sandra Bennink, Andreas von Bohl, Che J. Ngwa, Leonie Henschel, Andrea Kuehn, Nicole Pilch, Tim Weißbach, Alina N. Rosinski, Matthias Scheuermayer, Urska Repnik, Jude M. Przyborski, Allen M. Minns, Lindsey M. Orchard, Gareth Griffiths, Scott Eugene Lindner, Manuel Llinas, Gabriele Pradel

Research output: Contribution to journalArticle

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Abstract

The complex life-cycle of the human malaria parasite Plasmodium falciparum requires a high degree of tight coordination allowing the parasite to adapt to changing environments. One of the major challenges for the parasite is the human-to-mosquito transmission, which starts with the differentiation of blood stage parasites into the transmissible gametocytes, followed by the rapid conversion of the gametocytes into gametes, once they are taken up by the blood-feeding Anopheles vector. In order to pre-adapt to this change of host, the gametocytes store transcripts in stress granules that encode proteins needed for parasite development in the mosquito. Here we report on a novel stress granule component, the seven-helix protein 7-Helix-1. The protein, a homolog of the human stress response regulator LanC-like 2, accumulates in stress granules of female gametocytes and interacts with ribonucleoproteins, such as CITH, DOZI, and PABP1. Malaria parasites lacking 7-Helix-1 are significantly impaired in female gametogenesis and thus transmission to the mosquito. Lack of 7-Helix-1 further leads to a deregulation of components required for protein synthesis. Consistently, inhibitors of translation could mimic the 7-Helix-1 loss-of-function phenotype. 7-Helix-1 forms a complex with the RNA-binding protein Puf2, a translational regulator of the female-specific antigen Pfs25, as well as with pfs25-coding mRNA. In accord, gametocytes deficient of 7-Helix-1 exhibit impaired Pfs25 synthesis. Our data demonstrate that 7-Helix-1 constitutes stress granules crucial for regulating the synthesis of proteins needed for life-cycle progression of Plasmodium in the mosquito vector.

Original languageEnglish (US)
Article numbere1007249
JournalPLoS Pathogens
Volume14
Issue number8
DOIs
StatePublished - Aug 1 2018

Fingerprint

Plasmodium falciparum
Heat-Shock Proteins
Culicidae
Parasites
Proteins
Life Cycle Stages
Gametogenesis
Anopheles
Ribonucleoproteins
RNA-Binding Proteins
Plasmodium
Falciparum Malaria
Germ Cells
Malaria
Phenotype
Antigens
Messenger RNA

All Science Journal Classification (ASJC) codes

  • Parasitology
  • Microbiology
  • Immunology
  • Molecular Biology
  • Genetics
  • Virology

Cite this

Bennink, Sandra ; von Bohl, Andreas ; Ngwa, Che J. ; Henschel, Leonie ; Kuehn, Andrea ; Pilch, Nicole ; Weißbach, Tim ; Rosinski, Alina N. ; Scheuermayer, Matthias ; Repnik, Urska ; Przyborski, Jude M. ; Minns, Allen M. ; Orchard, Lindsey M. ; Griffiths, Gareth ; Lindner, Scott Eugene ; Llinas, Manuel ; Pradel, Gabriele. / A seven-helix protein constitutes stress granules crucial for regulating translation during human-to-mosquito transmission of Plasmodium falciparum. In: PLoS Pathogens. 2018 ; Vol. 14, No. 8.
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title = "A seven-helix protein constitutes stress granules crucial for regulating translation during human-to-mosquito transmission of Plasmodium falciparum",
abstract = "The complex life-cycle of the human malaria parasite Plasmodium falciparum requires a high degree of tight coordination allowing the parasite to adapt to changing environments. One of the major challenges for the parasite is the human-to-mosquito transmission, which starts with the differentiation of blood stage parasites into the transmissible gametocytes, followed by the rapid conversion of the gametocytes into gametes, once they are taken up by the blood-feeding Anopheles vector. In order to pre-adapt to this change of host, the gametocytes store transcripts in stress granules that encode proteins needed for parasite development in the mosquito. Here we report on a novel stress granule component, the seven-helix protein 7-Helix-1. The protein, a homolog of the human stress response regulator LanC-like 2, accumulates in stress granules of female gametocytes and interacts with ribonucleoproteins, such as CITH, DOZI, and PABP1. Malaria parasites lacking 7-Helix-1 are significantly impaired in female gametogenesis and thus transmission to the mosquito. Lack of 7-Helix-1 further leads to a deregulation of components required for protein synthesis. Consistently, inhibitors of translation could mimic the 7-Helix-1 loss-of-function phenotype. 7-Helix-1 forms a complex with the RNA-binding protein Puf2, a translational regulator of the female-specific antigen Pfs25, as well as with pfs25-coding mRNA. In accord, gametocytes deficient of 7-Helix-1 exhibit impaired Pfs25 synthesis. Our data demonstrate that 7-Helix-1 constitutes stress granules crucial for regulating the synthesis of proteins needed for life-cycle progression of Plasmodium in the mosquito vector.",
author = "Sandra Bennink and {von Bohl}, Andreas and Ngwa, {Che J.} and Leonie Henschel and Andrea Kuehn and Nicole Pilch and Tim Wei{\ss}bach and Rosinski, {Alina N.} and Matthias Scheuermayer and Urska Repnik and Przyborski, {Jude M.} and Minns, {Allen M.} and Orchard, {Lindsey M.} and Gareth Griffiths and Lindner, {Scott Eugene} and Manuel Llinas and Gabriele Pradel",
year = "2018",
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Bennink, S, von Bohl, A, Ngwa, CJ, Henschel, L, Kuehn, A, Pilch, N, Weißbach, T, Rosinski, AN, Scheuermayer, M, Repnik, U, Przyborski, JM, Minns, AM, Orchard, LM, Griffiths, G, Lindner, SE, Llinas, M & Pradel, G 2018, 'A seven-helix protein constitutes stress granules crucial for regulating translation during human-to-mosquito transmission of Plasmodium falciparum', PLoS Pathogens, vol. 14, no. 8, e1007249. https://doi.org/10.1371/journal.ppat.1007249

A seven-helix protein constitutes stress granules crucial for regulating translation during human-to-mosquito transmission of Plasmodium falciparum. / Bennink, Sandra; von Bohl, Andreas; Ngwa, Che J.; Henschel, Leonie; Kuehn, Andrea; Pilch, Nicole; Weißbach, Tim; Rosinski, Alina N.; Scheuermayer, Matthias; Repnik, Urska; Przyborski, Jude M.; Minns, Allen M.; Orchard, Lindsey M.; Griffiths, Gareth; Lindner, Scott Eugene; Llinas, Manuel; Pradel, Gabriele.

In: PLoS Pathogens, Vol. 14, No. 8, e1007249, 01.08.2018.

Research output: Contribution to journalArticle

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T1 - A seven-helix protein constitutes stress granules crucial for regulating translation during human-to-mosquito transmission of Plasmodium falciparum

AU - Bennink, Sandra

AU - von Bohl, Andreas

AU - Ngwa, Che J.

AU - Henschel, Leonie

AU - Kuehn, Andrea

AU - Pilch, Nicole

AU - Weißbach, Tim

AU - Rosinski, Alina N.

AU - Scheuermayer, Matthias

AU - Repnik, Urska

AU - Przyborski, Jude M.

AU - Minns, Allen M.

AU - Orchard, Lindsey M.

AU - Griffiths, Gareth

AU - Lindner, Scott Eugene

AU - Llinas, Manuel

AU - Pradel, Gabriele

PY - 2018/8/1

Y1 - 2018/8/1

N2 - The complex life-cycle of the human malaria parasite Plasmodium falciparum requires a high degree of tight coordination allowing the parasite to adapt to changing environments. One of the major challenges for the parasite is the human-to-mosquito transmission, which starts with the differentiation of blood stage parasites into the transmissible gametocytes, followed by the rapid conversion of the gametocytes into gametes, once they are taken up by the blood-feeding Anopheles vector. In order to pre-adapt to this change of host, the gametocytes store transcripts in stress granules that encode proteins needed for parasite development in the mosquito. Here we report on a novel stress granule component, the seven-helix protein 7-Helix-1. The protein, a homolog of the human stress response regulator LanC-like 2, accumulates in stress granules of female gametocytes and interacts with ribonucleoproteins, such as CITH, DOZI, and PABP1. Malaria parasites lacking 7-Helix-1 are significantly impaired in female gametogenesis and thus transmission to the mosquito. Lack of 7-Helix-1 further leads to a deregulation of components required for protein synthesis. Consistently, inhibitors of translation could mimic the 7-Helix-1 loss-of-function phenotype. 7-Helix-1 forms a complex with the RNA-binding protein Puf2, a translational regulator of the female-specific antigen Pfs25, as well as with pfs25-coding mRNA. In accord, gametocytes deficient of 7-Helix-1 exhibit impaired Pfs25 synthesis. Our data demonstrate that 7-Helix-1 constitutes stress granules crucial for regulating the synthesis of proteins needed for life-cycle progression of Plasmodium in the mosquito vector.

AB - The complex life-cycle of the human malaria parasite Plasmodium falciparum requires a high degree of tight coordination allowing the parasite to adapt to changing environments. One of the major challenges for the parasite is the human-to-mosquito transmission, which starts with the differentiation of blood stage parasites into the transmissible gametocytes, followed by the rapid conversion of the gametocytes into gametes, once they are taken up by the blood-feeding Anopheles vector. In order to pre-adapt to this change of host, the gametocytes store transcripts in stress granules that encode proteins needed for parasite development in the mosquito. Here we report on a novel stress granule component, the seven-helix protein 7-Helix-1. The protein, a homolog of the human stress response regulator LanC-like 2, accumulates in stress granules of female gametocytes and interacts with ribonucleoproteins, such as CITH, DOZI, and PABP1. Malaria parasites lacking 7-Helix-1 are significantly impaired in female gametogenesis and thus transmission to the mosquito. Lack of 7-Helix-1 further leads to a deregulation of components required for protein synthesis. Consistently, inhibitors of translation could mimic the 7-Helix-1 loss-of-function phenotype. 7-Helix-1 forms a complex with the RNA-binding protein Puf2, a translational regulator of the female-specific antigen Pfs25, as well as with pfs25-coding mRNA. In accord, gametocytes deficient of 7-Helix-1 exhibit impaired Pfs25 synthesis. Our data demonstrate that 7-Helix-1 constitutes stress granules crucial for regulating the synthesis of proteins needed for life-cycle progression of Plasmodium in the mosquito vector.

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