TY - JOUR
T1 - 20S proteasomes secreted by the malaria parasite promote its growth
AU - Dekel, Elya
AU - Yaffe, Dana
AU - Rosenhek-Goldian, Irit
AU - Ben-Nissan, Gili
AU - Ofir-Birin, Yifat
AU - Morandi, Mattia I.
AU - Ziv, Tamar
AU - Sisquella, Xavier
AU - Pimentel, Matthew A.
AU - Nebl, Thomas
AU - Kapp, Eugene
AU - Ohana Daniel, Yael
AU - Karam, Paula Abou
AU - Alfandari, Daniel
AU - Rotkopf, Ron
AU - Malihi, Shimrit
AU - Temin, Tal Block
AU - Mullick, Debakshi
AU - Revach, Or Yam
AU - Rudik, Ariel
AU - Gov, Nir S.
AU - Azuri, Ido
AU - Porat, Ziv
AU - Bergamaschi, Giulia
AU - Sorkin, Raya
AU - Wuite, Gijs J.L.
AU - Avinoam, Ori
AU - Carvalho, Teresa G.
AU - Cohen, Sidney R.
AU - Sharon, Michal
AU - Regev-Rudzki, Neta
N1 - Publisher Copyright:
© 2021, The Author(s).
PY - 2021/12/1
Y1 - 2021/12/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85101243350&partnerID=8YFLogxK
U2 - 10.1038/s41467-021-21344-8
DO - 10.1038/s41467-021-21344-8
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C2 - 33608523
AN - SCOPUS:85101243350
SN - 2041-1723
VL - 12
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 1172
ER -