Nature communications · 2021
20S proteasomes secreted by the malaria parasite promote its growth.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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Dekel Elya, Yaffe Dana, Rosenhek-Goldian Irit, Ben-Nissan Gili, Ofir-Birin Yifat, Morandi Mattia I, Ziv Tamar, Sisquella Xavier, Pimentel Matthew A, Nebl Thomas, Kapp Eugene, Ohana Daniel Yael, Karam Paula Abou, Alfandari Daniel, Rotkopf Ron, Malihi Shimrit, Temin Tal Block, Mullick Debakshi, Revach Or-Yam, Rudik Ariel, Gov Nir S, Azuri Ido, Porat Ziv, Bergamaschi Giulia, Sorkin Raya, Wuite Gijs J L, Avinoam Ori, Carvalho Teresa G, Cohen Sidney R, Sharon Michal, Regev-Rudzki Neta
Аннотация
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.