Hemoglobin S and C affect protein export in Plasmodium falciparum-infected erythrocytes
Malaria is a potentially deadly disease. However, not every infected person develops severe symptoms. Some people are protected by naturally occurring mechanisms that frequently involve inheritable modifications in their hemoglobin. The best studied protective hemoglobins are the sickle cell hemoglo...
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doaj-cafa07666a7b46559576669e89433af32021-06-02T18:47:12ZengThe Company of BiologistsBiology Open2046-63902015-02-014340041010.1242/bio.201410942201410942Hemoglobin S and C affect protein export in Plasmodium falciparum-infected erythrocytesNicole Kilian0Sirikamol Srismith1Martin Dittmer2Djeneba Ouermi3Cyrille Bisseye4Jacques Simpore5Marek Cyrklaff6Cecilia P. Sanchez7Michael Lanzer8 Center of Infectious Diseases, Parasitology, Heidelberg University, Im Neuenheimer Feld 324, 69120 Heidelberg, Germany Center of Infectious Diseases, Parasitology, Heidelberg University, Im Neuenheimer Feld 324, 69120 Heidelberg, Germany Center of Infectious Diseases, Parasitology, Heidelberg University, Im Neuenheimer Feld 324, 69120 Heidelberg, Germany Biomolecular Research Center Pietro Annigoni, University of Ouagadougou, 01 BP 364 Ouagadougou, Burkina Faso Biomolecular Research Center Pietro Annigoni, University of Ouagadougou, 01 BP 364 Ouagadougou, Burkina Faso Biomolecular Research Center Pietro Annigoni, University of Ouagadougou, 01 BP 364 Ouagadougou, Burkina Faso Center of Infectious Diseases, Parasitology, Heidelberg University, Im Neuenheimer Feld 324, 69120 Heidelberg, Germany Center of Infectious Diseases, Parasitology, Heidelberg University, Im Neuenheimer Feld 324, 69120 Heidelberg, Germany Center of Infectious Diseases, Parasitology, Heidelberg University, Im Neuenheimer Feld 324, 69120 Heidelberg, Germany Malaria is a potentially deadly disease. However, not every infected person develops severe symptoms. Some people are protected by naturally occurring mechanisms that frequently involve inheritable modifications in their hemoglobin. The best studied protective hemoglobins are the sickle cell hemoglobin (HbS) and hemoglobin C (HbC) which both result from a single amino acid substitution in β-globin: glutamic acid at position 6 is replaced by valine or lysine, respectively. How these hemoglobinopathies protect from severe malaria is only partly understood. Models currently proposed in the literature include reduced disease-mediating cytoadherence of parasitized hemoglobinopathic erythrocytes, impaired intraerythrocytic development of the parasite, dampened inflammatory responses, or a combination thereof. Using a conditional protein export system and tightly synchronized Plasmodium falciparum cultures, we now show that export of parasite-encoded proteins across the parasitophorous vacuolar membrane is delayed, slower, and reduced in amount in hemoglobinopathic erythrocytes as compared to parasitized wild type red blood cells. Impaired protein export affects proteins targeted to the host cell cytoplasm, Maurer's clefts, and the host cell plasma membrane. Impaired protein export into the host cell compartment provides a mechanistic explanation for the reduced cytoadherence phenotype associated with parasitized hemoglobinopathic erythrocytes.http://bio.biologists.org/content/4/3/400HemoglobinopathyProtein exportMalariaP. falciparum |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Nicole Kilian Sirikamol Srismith Martin Dittmer Djeneba Ouermi Cyrille Bisseye Jacques Simpore Marek Cyrklaff Cecilia P. Sanchez Michael Lanzer |
spellingShingle |
Nicole Kilian Sirikamol Srismith Martin Dittmer Djeneba Ouermi Cyrille Bisseye Jacques Simpore Marek Cyrklaff Cecilia P. Sanchez Michael Lanzer Hemoglobin S and C affect protein export in Plasmodium falciparum-infected erythrocytes Biology Open Hemoglobinopathy Protein export Malaria P. falciparum |
author_facet |
Nicole Kilian Sirikamol Srismith Martin Dittmer Djeneba Ouermi Cyrille Bisseye Jacques Simpore Marek Cyrklaff Cecilia P. Sanchez Michael Lanzer |
author_sort |
Nicole Kilian |
title |
Hemoglobin S and C affect protein export in Plasmodium falciparum-infected erythrocytes |
title_short |
Hemoglobin S and C affect protein export in Plasmodium falciparum-infected erythrocytes |
title_full |
Hemoglobin S and C affect protein export in Plasmodium falciparum-infected erythrocytes |
title_fullStr |
Hemoglobin S and C affect protein export in Plasmodium falciparum-infected erythrocytes |
title_full_unstemmed |
Hemoglobin S and C affect protein export in Plasmodium falciparum-infected erythrocytes |
title_sort |
hemoglobin s and c affect protein export in plasmodium falciparum-infected erythrocytes |
publisher |
The Company of Biologists |
series |
Biology Open |
issn |
2046-6390 |
publishDate |
2015-02-01 |
description |
Malaria is a potentially deadly disease. However, not every infected person develops severe symptoms. Some people are protected by naturally occurring mechanisms that frequently involve inheritable modifications in their hemoglobin. The best studied protective hemoglobins are the sickle cell hemoglobin (HbS) and hemoglobin C (HbC) which both result from a single amino acid substitution in β-globin: glutamic acid at position 6 is replaced by valine or lysine, respectively. How these hemoglobinopathies protect from severe malaria is only partly understood. Models currently proposed in the literature include reduced disease-mediating cytoadherence of parasitized hemoglobinopathic erythrocytes, impaired intraerythrocytic development of the parasite, dampened inflammatory responses, or a combination thereof. Using a conditional protein export system and tightly synchronized Plasmodium falciparum cultures, we now show that export of parasite-encoded proteins across the parasitophorous vacuolar membrane is delayed, slower, and reduced in amount in hemoglobinopathic erythrocytes as compared to parasitized wild type red blood cells. Impaired protein export affects proteins targeted to the host cell cytoplasm, Maurer's clefts, and the host cell plasma membrane. Impaired protein export into the host cell compartment provides a mechanistic explanation for the reduced cytoadherence phenotype associated with parasitized hemoglobinopathic erythrocytes. |
topic |
Hemoglobinopathy Protein export Malaria P. falciparum |
url |
http://bio.biologists.org/content/4/3/400 |
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