Author
Listed:
- Elya Dekel
(Weizmann Institute of Science)
- Dana Yaffe
(Weizmann Institute of Science)
- Irit Rosenhek-Goldian
(Weizmann Institute of Science)
- Gili Ben-Nissan
(Weizmann Institute of Science)
- Yifat Ofir-Birin
(Weizmann Institute of Science)
- Mattia I. Morandi
(Weizmann Institute of Science)
- Tamar Ziv
(Technion - Israel Institute of Technology)
- Xavier Sisquella
(The Walter and Eliza Hall Institute of Medical Research
The University of Melbourne)
- Matthew A. Pimentel
(The Walter and Eliza Hall Institute of Medical Research
The University of Melbourne)
- Thomas Nebl
(The Walter and Eliza Hall Institute of Medical Research
The University of Melbourne)
- Eugene Kapp
(The Walter and Eliza Hall Institute of Medical Research
The University of Melbourne)
- Yael Ohana Daniel
(Weizmann Institute of Science)
- Paula Abou Karam
(Weizmann Institute of Science)
- Daniel Alfandari
(Weizmann Institute of Science)
- Ron Rotkopf
(Weizmann Institute of Science)
- Shimrit Malihi
(Weizmann Institute of Science)
- Tal Block Temin
(Weizmann Institute of Science)
- Debakshi Mullick
(Weizmann Institute of Science)
- Or-Yam Revach
(Weizmann Institute of Science)
- Ariel Rudik
(Weizmann Institute of Science)
- Nir S. Gov
(Weizmann Institute of Science)
- Ido Azuri
(Weizmann Institute of Science)
- Ziv Porat
(Flow Cytometry Unit, Life Sciences Core Facilities, Weizmann Institute of Science)
- Giulia Bergamaschi
(Vrije Universiteit Amsterdam)
- Raya Sorkin
(Tel Aviv University
Tel Aviv University)
- Gijs J. L. Wuite
(Vrije Universiteit Amsterdam)
- Ori Avinoam
(Weizmann Institute of Science)
- Teresa G. Carvalho
(La Trobe University)
- Sidney R. Cohen
(Weizmann Institute of Science)
- Michal Sharon
(Weizmann Institute of Science)
- Neta Regev-Rudzki
(Weizmann Institute of Science)
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.
Suggested Citation
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 D, 2021.
"20S proteasomes secreted by the malaria parasite promote its growth,"
Nature Communications, Nature, vol. 12(1), pages 1-19, December.
Handle:
RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-21344-8
DOI: 10.1038/s41467-021-21344-8
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