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  3. 20S proteasomes secreted by the malaria parasite promote its growth

20S proteasomes secreted by the malaria parasite promote its growth

  • Nat Commun. 2021 Feb 19;12(1):1172. doi: 10.1038/s41467-021-21344-8.
Elya Dekel  # 1,  Dana Yaffe  # 1,  Irit Rosenhek-Goldian 2,  Gili Ben-Nissan 1,  Yifat Ofir-Birin 1,  Mattia I Morandi 1,  Tamar Ziv 3,  Xavier Sisquella 4 5,  Matthew A Pimentel 4 5,  Thomas Nebl 4 5,  Eugene Kapp 4 5,  Yael Ohana Daniel 1,  Paula Abou Karam 1,  Daniel Alfandari 1,  Ron Rotkopf 6,  Shimrit Malihi 1,  Tal Block Temin 1,  Debakshi Mullick 6,  Or-Yam Revach 1,  Ariel Rudik 1,  Nir S Gov 7,  Ido Azuri 6,  Ziv Porat 8,  Giulia Bergamaschi 9,  Raya Sorkin 10 11,  Gijs J L Wuite 9,  Ori Avinoam 1,  Teresa G Carvalho 12,  Sidney R Cohen 2,  Michal Sharon 13,  Neta Regev-Rudzki 14
Affiliations

Affiliations

  • 1 Department of Biomolecular Sciences, Weizmann Institute of Science, Rehovot, 7610001, Israel.
  • 2 Department of Chemical Research Support, Weizmann Institute of Science, Rehovot, 7610001, Israel.
  • 3 Smoler Proteomics Center, Department of Biology, Technion - Israel Institute of Technology, Haifa, Israel.
  • 4 The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, VIC, 3052, Australia.
  • 5 Department of Medical Biology, The University of Melbourne, Grattan Street, Parkville, VIC, 3010, Australia.
  • 6 Bioinformatics Unit, Department of Life Sciences Core Facilities, Weizmann Institute of Science, Rehovot, 7610001, Israel.
  • 7 Department of Chemical and Biological Physics, Weizmann Institute of Science, Rehovot, 7610001, Israel.
  • 8 Flow Cytometry Unit, Life Sciences Core Facilities, Weizmann Institute of Science, Rehovot, 7610001, Israel.
  • 9 Department of Physics and Astronomy and LaserLab, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands.
  • 10 School of Chemistry, Tel Aviv University, Tel Aviv, Israel.
  • 11 Center for Physics and Chemistry of Living Systems, Tel Aviv University, Tel Aviv, Israel.
  • 12 Department of Physiology, Anatomy and Microbiology, La Trobe University, Melbourne, VIC, 3086, Australia.
  • 13 Department of Biomolecular Sciences, Weizmann Institute of Science, Rehovot, 7610001, Israel. michal.sharon@weizmann.ac.il.
  • 14 Department of Biomolecular Sciences, Weizmann Institute of Science, Rehovot, 7610001, Israel. neta.regev-rudzki@weizmann.ac.il.
  • # Contributed equally.
PMID: 33608523 DOI: 10.1038/s41467-021-21344-8
Abstract

Mature red blood cells (RBCs) lack internal organelles and canonical defense mechanisms, making them both a fascinating host cell, in general, and an intriguing choice for the deadly malaria parasite Plasmodium falciparum (Pf), in particular. Pf, while growing inside its natural host, the human RBC, secretes multipurpose extracellular vesicles (EVs), yet their influence on this essential host cell remains unknown. Here we demonstrate that Pf parasites, cultured in fresh human donor blood, secrete within such EVs assembled and functional 20S Proteasome complexes (EV-20S). The EV-20S proteasomes modulate the mechanical properties of naïve human RBCs by remodeling their cytoskeletal network. Furthermore, we identify four degradation targets of the secreted 20S Proteasome, the phosphorylated cytoskeletal proteins β-adducin, ankyrin-1, dematin and Epb4.1. Overall, our findings reveal a previously unknown 20S Proteasome secretion mechanism employed by the human malaria Parasite, which primes RBCs for Parasite invasion by altering membrane stiffness, to facilitate malaria Parasite growth.

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