PV1 Protein from Plasmodium falciparum Exhibits Chaperone-Like Functions and Cooperates with Hsp100s

Hakamada, Kazuaki; Nakamura, Manami; Shinohara, Kyosuke; Noguchi, Keiichi; Nagaoka, Hikaru; Takashima, Eizo; Morishima, Ken; Inoue, Rintaro; Sugiyama, Masaaki; Kawamoto, Akihiro; Yohda, Masafumi

doi:10.3390/ijms21228616

Cited by 7 publications

(3 citation statements)

References 50 publications

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“…Refolding of effector proteins happens in the host, although the mechanisms behind this process are not fully understood. Host proteins and exported parasite chaperones, such as HSP40 and HSP70, are thought to play a role (Hakamada et al, 2020; Külzer et al, 2012). GRA17 and GRA23 are related to Plasmodium EXP2.…”

Section: Functions Of Dense Granule (Gra) Proteinsmentioning

confidence: 99%

Dense granule biogenesis, secretion, and function in Toxoplasma gondii

Griffith

Pearce

Heaslip

2022

J Eukaryotic Microbiology

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Toxoplasma gondii is an obligate intracellular parasite and the causative agent of Toxoplasmosis. A key to understanding and treating the disease lies with determining how the parasite can survive and replicate within cells of its host. Proteins released from specialized secretory vesicles, named the dense granules (DGs), have diverse functions that are critical for adapting the intracellular environment, and are thus key to survival and pathogenicity. In this review, we describe the current understanding and outstanding questions regarding dense granule biogenesis, trafficking, and regulation of secretion. In addition, we provide an overview of dense granule protein (“GRA”) function upon secretion, with a focus on proteins that have recently been identified.

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Section: Functions Of Dense Granule (Gra) Proteinsmentioning

confidence: 99%

Dense granule biogenesis, secretion, and function in Toxoplasma gondii

Griffith

Pearce

Heaslip

2022

J Eukaryotic Microbiology

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“…making inference to specific functions difficult, although TRX2 is an active thioredoxin which has been suggested to aid in remodeling disulfide bonds to mediate unfolding of exported cargo or regulation of PTEX [ 29 , 38 – 40 ]. Additionally, although unrelated to known chaperones, PV1 has been proposed to assist PTEX as a co-chaperone based on its ability to replace HSP40 in a refolding chaperone system comprised of HSP70, HSP40, and the HSP101-related disaggregase HSP104 (all from Chaetomium termophilum ) [ 41 ]. While these proteins can be disrupted or conditionally depleted during in vitro culture (most with little to no observable impact on protein export or parasite fitness), these accessory factors appear to aid in export of effector subsets that are important in the context of the vertebrate host, and some are crucial in vivo [ 29 , 37 , 40 , 42 – 44 ].…”

Section: Protein Exportmentioning

confidence: 99%

Transport mechanisms at the malaria parasite-host cell interface

Beck

2021

PLoS Pathog

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Obligate intracellular malaria parasites reside within a vacuolar compartment generated during invasion which is the principal interface between pathogen and host. To subvert their host cell and support their metabolism, these parasites coordinate a range of transport activities at this membrane interface that are critically important to parasite survival and virulence, including nutrient import, waste efflux, effector protein export, and uptake of host cell cytosol. Here, we review our current understanding of the transport mechanisms acting at the malaria parasite vacuole during the blood and liver-stages of development with a particular focus on recent advances in our understanding of effector protein translocation into the host cell by the Plasmodium Translocon of EXported proteins (PTEX) and small molecule transport by the PTEX membrane-spanning pore EXP2. Comparison to Toxoplasma gondii and other related apicomplexans is provided to highlight how similar and divergent mechanisms are employed to fulfill analogous transport activities.

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“…Recently an additional complex residing within the PV space has been found to interact with PTEX: the exported protein‐interacting complex (EPIC) (Batinovic et al, 2017; Hakamada et al, 2020; Morita et al, 2018). EPIC consists of three proteins, PV1/PV2/EXP3, and has been linked to PfEMP1 trafficking across the PVM via an auxiliary interaction with PTEX (Batinovic et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

The Plasmodium falciparum parasitophorous vacuole protein P113 interacts with the parasite protein export machinery and maintains normal vacuole architecture

Bullen

Sanders

Dans

et al. 2022

Molecular Microbiology

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Infection with Plasmodium falciparum parasites results in approximately 627,000 deaths from malaria annually. Key to the parasite’s success is their ability to invade and subsequently grow within human erythrocytes. Parasite proteins involved in parasite invasion and proliferation are therefore intrinsically of great interest, as targeting these proteins could provide novel means of therapeutic intervention. One such protein is P113 which has been reported to be both an invasion protein and an intracellular protein located within the parasitophorous vacuole (PV). The PV is delimited by a membrane (PVM) across which a plethora of parasite‐specific proteins are exported via the Plasmodium Translocon of Exported proteins (PTEX) into the erythrocyte to enact various immune evasion functions. To better understand the role of P113 we isolated its binding partners from in vitro cultures of P. falciparum. We detected interactions with the protein export machinery (PTEX and exported protein‐interacting complex) and a variety of proteins that either transit through the PV or reside on the parasite plasma membrane. Genetic knockdown or partial deletion of P113 did not significantly reduce parasite growth or protein export but did disrupt the morphology of the PVM, suggesting that P113 may play a role in maintaining normal PVM architecture.

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PV1 Protein from Plasmodium falciparum Exhibits Chaperone-Like Functions and Cooperates with Hsp100s

Cited by 7 publications

References 50 publications

Dense granule biogenesis, secretion, and function in Toxoplasma gondii

Dense granule biogenesis, secretion, and function in Toxoplasma gondii

Transport mechanisms at the malaria parasite-host cell interface

The Plasmodium falciparum parasitophorous vacuole protein P113 interacts with the parasite protein export machinery and maintains normal vacuole architecture

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