Dataset Information

20S proteasomes exported 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, export 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 novel degradation targets of the exported 20S proteasome, the phosphorylated cytoskeletal proteins β-adducin, ankyrin-1, dematin and Epb4.1. Overall, our findings reveal a previously unknown 20S proteasome export mechanism employed by the human malaria parasite, which primes RBCs for parasite invasion by altering membrane stiffness, to facilitate malaria parasite growth.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Plasmodium Falciparum (isolate 3d7)

TISSUE(S): Erythrocyte, Blood

DISEASE(S): Plasmodium Falciparum Malaria

SUBMITTER: Eugene Kapp

LAB HEAD: Neta Regev-Rudzki

PROVIDER: PXD023353 | Pride | 2021-02-04

REPOSITORIES: Pride

ACCESS DATA

Dataset's files

Source:

Items per page:

1 - 5 of 40

Publications

20S proteasomes secreted by the malaria parasite promote its growth.

Dekel Elya E Yaffe Dana D Rosenhek-Goldian Irit I Ben-Nissan Gili G Ofir-Birin Yifat Y Morandi Mattia I MI Ziv Tamar T Sisquella Xavier X Pimentel Matthew A MA Nebl Thomas T Kapp Eugene E Ohana Daniel Yael Y Karam Paula Abou PA Alfandari Daniel D Rotkopf Ron R Malihi Shimrit S Temin Tal Block TB Mullick Debakshi D Revach Or-Yam OY Rudik Ariel A Gov Nir S NS Azuri Ido I Porat Ziv Z Bergamaschi Giulia G Sorkin Raya R Wuite Gijs J L GJL Avinoam Ori O Carvalho Teresa G TG Cohen Sidney R SR Sharon Michal M Regev-Rudzki Neta N

Nature communications 20210219 1

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, secret ...[more]

PMID: 33608523

Similar Datasets

Project description:During intra-erythrocytic development, late asexually replicating Plasmodium falciparum parasites sequester from peripheral circulation. This facilitates chronic infection and is linked to severe disease and organ-specific pathology including cerebral and placental malaria. Immature gametocytes M-bM-^@M-^S sexual stage precursor cells M-bM-^@M-^S likewise disappear from circulation. Recent work has demonstrated that these sexual stage parasites are located in the hematopoietic system of the bone marrow before mature gametocytes are released into the blood stream to facilitate mosquito transmission. However, as sequestration occurs only in vivo and not during in vitro culture, the mechanisms by which it is regulated and enacted (particularly by the gametocyte stage) remain poorly understood. We generated the most comprehensive P. falciparum functional gene network to date by integrating global transcriptional data from a large set of asexual and sexual in vitro samples, patient-derived in vivo samples, and a new set of in vitro samples profiling sexual commitment. We defined more than 250 functional modules (clusters) of genes that are co-expressed primarily during the intra-erythrocytic parasite cycle, including 35 during sexual commitment and gametocyte development. Comparing the in vivo and in vitro datasets allowed us, for the first time, to map the time point of asexual parasite sequestration in patients to 22 hours post invasion, confirming previous in vitro observations on the dynamics of host cell modification and cytoadherence. Moreover, we were able to define the properties of gametocyte sequestration, demonstrating the presence of two circulating gametocyte populations: gametocyte rings between 0 and ~30 hours post invasion and mature gametocytes after around 7 days post invasion. We used 164/TdTom, a transgenic parasite line expressing a red fluorescent protein reporter under a gametocyte-specific promoter to generate schizont samples. Schizonts were subsequently isolated from both the fluorescent and non-fluorescent population by FACS and prepared for microarray analysis. Two biological replicates were produced for both the fluorescent and the non-fluorescent samples.

			Action	DRS
	P1771_01.raw	Raw
	P1771_02.raw	Raw
	P1771_03.raw	Raw
	P1771_04.raw	Raw
	P1771_05.raw	Raw