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 Rudik; Nir 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

doi:10.1038/s41467-021-21344-8

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

Weizmann Institute of Science, Tel Aviv University, Technion - Israel Institute of Technology

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Article number	1172
Pages (from-to)	1172
Number of pages	19
Journal	Nature Communications
Volume	12
Issue number	1
Early online date	19 Feb 2021
DOIs	https://doi.org/10.1038/s41467-021-21344-8
State	Published - 1 Dec 2021

Keywords

Biological Transport/physiology
Cytoskeleton/metabolism
Erythrocytes/cytology
Host-Parasite Interactions/physiology
Humans
Malaria, Falciparum/metabolism
Membrane Proteins/metabolism
Phosphorylation
Plasmodium falciparum/growth & development
Proteasome Endopeptidase Complex/metabolism
Proteomics

All Science Journal Classification (ASJC) codes

General Chemistry
General Biochemistry,Genetics and Molecular Biology
General Physics and Astronomy

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/s41467-021-21344-8License: CC BY

nr_NatureComm_20SProteasomessecreted_PV_2021Final published version, 6.27 MBLicense: CC BY

Cite this

Dekel, E., Yaffe, D., Rosenhek-Goldian, I., Ben-Nissan, G., Ofir-Birin, Y., Morandi, M. I., Ziv, T., Sisquella, X., Pimentel, M. A., Nebl, T., Kapp, E., Ohana Daniel, Y., Karam, P. A., Alfandari, D., Rotkopf, R., Malihi, S., Temin, T. B., Mullick, D., Revach, O. Y., ... Regev-Rudzki, N. (2021). 20S proteasomes secreted by the malaria parasite promote its growth. Nature Communications, 12(1), 1172. Article 1172. https://doi.org/10.1038/s41467-021-21344-8

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title = "20S proteasomes secreted by the malaria parasite promote its growth",

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 na{\"i}ve 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.",

keywords = "Biological Transport/physiology, Cytoskeleton/metabolism, Erythrocytes/cytology, Host-Parasite Interactions/physiology, Humans, Malaria, Falciparum/metabolism, Membrane Proteins/metabolism, Phosphorylation, Plasmodium falciparum/growth & development, Proteasome Endopeptidase Complex/metabolism, Proteomics",

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

note = "Publisher Copyright: {\textcopyright} 2021, The Author(s).",

year = "2021",

month = dec,

day = "1",

doi = "10.1038/s41467-021-21344-8",

language = "الإنجليزيّة",

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Dekel, E, Yaffe, D, Rosenhek-Goldian, I, Ben-Nissan, G, Ofir-Birin, Y, Morandi, MI, Ziv, T, Sisquella, X, Pimentel, MA, Nebl, T, Kapp, E, Ohana Daniel, Y, Karam, PA, Alfandari, D, Rotkopf, R, Malihi, S, Temin, TB, Mullick, D, Revach, OY, Rudik, A, Gov, NS, Azuri, I, Porat, Z, Bergamaschi, G, Sorkin, R, Wuite, GJL, Avinoam, O, Carvalho, TG, Cohen, SR, Sharon, M & Regev-Rudzki, N 2021, '20S proteasomes secreted by the malaria parasite promote its growth', Nature Communications, vol. 12, no. 1, 1172, pp. 1172. https://doi.org/10.1038/s41467-021-21344-8

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

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.

KW - Biological Transport/physiology

KW - Cytoskeleton/metabolism

KW - Erythrocytes/cytology

KW - Host-Parasite Interactions/physiology

KW - Humans

KW - Malaria, Falciparum/metabolism

KW - Membrane Proteins/metabolism

KW - Phosphorylation

KW - Plasmodium falciparum/growth & development

KW - Proteasome Endopeptidase Complex/metabolism

KW - Proteomics

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

M3 - مقالة

C2 - 33608523

SN - 2041-1723

VL - 12

SP - 1172

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 1172

ER -

20S proteasomes secreted by the malaria parasite promote its growth

Abstract

Keywords

All Science Journal Classification (ASJC) codes

UN SDGs

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