Cholesterol-rich microdomains are membrane compartments characterized by specific lipid and protein composition. These dynamic assemblies are involved in several biological processes, including infection by intracellular pathogens. This work provides a comprehensive analysis of the composition of human erythrocyte membrane microdomains. Based on their floating properties, we also categorized the microdomain-associated proteins into clusters. Interestingly, erythrocyte microdomains include the vast majority of the proteins known to be involved in invasion by the malaria parasite Plasmodium falciparum. We show here that the Ecto-ADP-ribosyltransferase 4 (ART4) and Aquaporin 1 (AQP1), found within one specific cluster, containing the essential host determinant CD55, are recruited to the site of parasite entry and then internalized to the newly formed parasitophorous vacuole membrane. By generating null erythroid cell lines, we showed that one of these proteins, ART4, plays a role in P. falciparum invasion. We also found that genetic variants in both ART4 and AQP1 are associated with susceptibility to the disease in a malaria-endemic population.

Structural organization of erythrocyte membrane microdomains and their relation with malaria susceptibility / Olivieri, A.; Lee, R. S.; Fratini, F.; Keutcha, C.; Chaand, M.; Mangano, V.; Celani, F.; Mochi, S.; Birago, C.; Paone, S.; Grasso, F.; Tirelli, V.; Falchi, M.; Shabani, E.; Bertoncini, S.; Sirima, B. S.; Pizzi, E.; Modiano, D.; Duraisingh, M. T.; Ponzi, M.. - In: COMMUNICATIONS BIOLOGY. - ISSN 2399-3642. - 4:1(2021), pp. 1-10. [10.1038/s42003-021-02900-w]

Structural organization of erythrocyte membrane microdomains and their relation with malaria susceptibility

Mochi S.;Tirelli V.;Falchi M.;Modiano D.;
2021

Abstract

Cholesterol-rich microdomains are membrane compartments characterized by specific lipid and protein composition. These dynamic assemblies are involved in several biological processes, including infection by intracellular pathogens. This work provides a comprehensive analysis of the composition of human erythrocyte membrane microdomains. Based on their floating properties, we also categorized the microdomain-associated proteins into clusters. Interestingly, erythrocyte microdomains include the vast majority of the proteins known to be involved in invasion by the malaria parasite Plasmodium falciparum. We show here that the Ecto-ADP-ribosyltransferase 4 (ART4) and Aquaporin 1 (AQP1), found within one specific cluster, containing the essential host determinant CD55, are recruited to the site of parasite entry and then internalized to the newly formed parasitophorous vacuole membrane. By generating null erythroid cell lines, we showed that one of these proteins, ART4, plays a role in P. falciparum invasion. We also found that genetic variants in both ART4 and AQP1 are associated with susceptibility to the disease in a malaria-endemic population.
2021
erythrocyte membrane; erythrocytes; humans; malaria; malaria, falciparum; membrane microdomains; plasmodium falciparum
01 Pubblicazione su rivista::01a Articolo in rivista
Structural organization of erythrocyte membrane microdomains and their relation with malaria susceptibility / Olivieri, A.; Lee, R. S.; Fratini, F.; Keutcha, C.; Chaand, M.; Mangano, V.; Celani, F.; Mochi, S.; Birago, C.; Paone, S.; Grasso, F.; Tirelli, V.; Falchi, M.; Shabani, E.; Bertoncini, S.; Sirima, B. S.; Pizzi, E.; Modiano, D.; Duraisingh, M. T.; Ponzi, M.. - In: COMMUNICATIONS BIOLOGY. - ISSN 2399-3642. - 4:1(2021), pp. 1-10. [10.1038/s42003-021-02900-w]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1646463
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