2. Academic Validation
  3. Structural organization of erythrocyte membrane microdomains and their relation with malaria susceptibility

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

  • Commun Biol. 2021 Dec 8;4(1):1375. doi: 10.1038/s42003-021-02900-w.
Anna Olivieri 1,  Rebecca S Lee 2,  Federica Fratini 3,  Cyrianne Keutcha 2,  Mudit Chaand 2,  Valentina Mangano 4 5,  Francesco Celani 6,  Stefania Mochi 6,  Cecilia Birago 6,  Silvio Paone 6 4,  Felicia Grasso 6,  Valentina Tirelli 3,  Mario Falchi 7,  Estela Shabani 2,  Stefania Bertoncini 5 8,  Bienvenu Sodiomon Sirima 9,  Elisabetta Pizzi 3,  David Modiano 4,  Manoj T Duraisingh # 2,  Marta Ponzi # 6
Affiliations

Affiliations

  • 1 Dipartimento di Malattie Infettive, Istituto Superiore di Sanità, Rome, Italy. anna.olivieri@iss.it.
  • 2 Department of Immunology and Infectious Diseases, Harvard T. H. Chan School of Public Health, Boston, MA, USA.
  • 3 Servizio Grandi Strumentazioni e Core Facilities, Istituto Superiore di Sanità, Rome, Italy.
  • 4 Dipartimento di Sanità Pubblica e Malattie Infettive, Sapienza Università di Roma, Rome, Italy.
  • 5 Dept. of Traslational Research, University of Pisa, Pisa, Italy.
  • 6 Dipartimento di Malattie Infettive, Istituto Superiore di Sanità, Rome, Italy.
  • 7 National HIV/AIDS Research Center (CNAIDS), Istituto Superiore di Sanità, Rome, Italy.
  • 8 Department of Biology, University of Pisa, Pisa, Italy.
  • 9 Centre National de Recherche et de Formation sur le Paludisme (CNRFP), Ouagadougou, Burkina Faso.
  • # Contributed equally.
PMID: 34880413 DOI: 10.1038/s42003-021-02900-w
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.

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