20S proteasomes secreted by the malaria parasite promote its growth

Elya Dekel, Dana Yaffe, Irit Rosenhek-Goldian, Gili Ben-Nissan, Yifat Ofir-Birin, Mattia I. Morandi, Tamar Ziv, Xavier Sisquella, Matthew A. Pimentel, Thomas Nebl, Eugene Kapp, Yael Ohana Daniel, Paula Abou Karam, Daniel Alfandari, Ron Rotkopf, Shimrit Malihi, Tal Block Temin, Debakshi Mullick, Or Yam Revach, Ariel RudikNir S. Gov, Ido Azuri, Ziv Porat, Giulia Bergamaschi, Raya Sorkin, Gijs J.L. Wuite, Ori Avinoam, Teresa G. Carvalho, Sidney R. Cohen, Michal Sharon*, Neta Regev-Rudzki*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

42 Scopus citations


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.

Original languageEnglish
Article number1172
JournalNature Communications
Issue number1
StatePublished - 1 Dec 2021


FundersFunder number
Benoziyo Endowment Fund for the Advancement of Science
Jeanne and Joseph Nissim Center for Life Sciences Research
Jeanne and Joseph Nissim Foundation for Life Sciences Research
Horizon 2020 Framework Programme
H2020 European Research Council757743
European Research Council
Israel Science Foundation2235/16, 619/16
Horizon 2020300/17, 636752


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