The Plasmodium falciparum Artemisinin Susceptibility-Associated AP-2 Adaptin μ Subunit is Clathrin Independent and Essential for Schizont Maturation

Author:

Henrici Ryan C.1,Edwards Rachel L.2,Zoltner Martin3,van Schalkwyk Donelly A.1,Hart Melissa N.14,Mohring Franziska1,Moon Robert W.1,Nofal Stephanie D.5,Patel Avnish5,Flueck Christian5,Baker David A.5ORCID,Odom John Audrey R.26,Field Mark C.37,Sutherland Colin J.18ORCID

Affiliation:

1. Department of Infection Biology, Faculty of Infectious Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom

2. Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri, USA

3. School of Life Sciences, University of Dundee, Dundee, United Kingdom

4. Department of Crystallography, Birkbeck, University of London, London, United Kingdom

5. Department of Pathogen Molecular Biology, Faculty of Infectious Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom

6. Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri, USA

7. Biology Centre, Institute of Parasitology, Czech Academy of Sciences, Budweis, Czech Republic

8. PHE Malaria Reference Laboratory, London School of Hygiene and Tropical Medicine, London, United Kingdom

Abstract

We examine in detail the AP-2 adaptin complex from the malaria parasite Plasmodium falciparum . In most studied organisms, AP-2 is involved in bringing material into the cell from outside, a process called endocytosis. Previous work shows that changes to the μ subunit of AP-2 can contribute to drug resistance. Our experiments show that AP-2 is essential for parasite development in blood but does not have any role in clathrin-mediated endocytosis. This suggests that a specialized function for AP-2 has developed in malaria parasites, and this may be important for understanding its impact on drug resistance.

Funder

HHS | National Institutes of Health

Public Health England

Medicines for Malaria Venture

Wellcome Trust

UK Research and Innovation | Medical Research Council

Publisher

American Society for Microbiology

Subject

Virology,Microbiology

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