| Literature DB >> 33608523 |
Elya Dekel1, Dana Yaffe1, Irit Rosenhek-Goldian2, Gili Ben-Nissan1, Yifat Ofir-Birin1, Mattia I Morandi1, Tamar Ziv3, Xavier Sisquella4,5, Matthew A Pimentel4,5, Thomas Nebl4,5, Eugene Kapp4,5, Yael Ohana Daniel1, Paula Abou Karam1, Daniel Alfandari1, Ron Rotkopf6, Shimrit Malihi1, Tal Block Temin1, Debakshi Mullick6, Or-Yam Revach1, Ariel Rudik1, Nir S Gov7, Ido Azuri6, Ziv Porat8, Giulia Bergamaschi9, Raya Sorkin10,11, Gijs J L Wuite9, Ori Avinoam1, Teresa G Carvalho12, Sidney R Cohen2, Michal Sharon13, Neta Regev-Rudzki14.
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.Entities:
Year: 2021 PMID： 33608523 DOI： 10.1038/s41467-021-21344-8
Source DB: PubMed Journal: Nat Commun ISSN： 2041-1723 Impact factor: 14.919