Small heat shock proteins in cellular adhesion and migration

Montagna, Georgina N.; Matuschewski, Kai; Buscaglia, Carlos A.

doi:10.4161/cam.20101

Cited by 12 publications

(7 citation statements)

References 66 publications

(99 reference statements)

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“…This finding using two developmental stages of sporozoites provides independent support for our previous experimental genetics evidence that fast and continuous gliding locomotion is only important for intradermal migration and not for hepatocyte invasion in vitro and in vivo (32). In hsp20(Ϫ) sporozoites, speed and cellular adhesion is dramatically altered, resulting in impaired natural malaria transmission but perfectly normal host cell invasion (32,50).…”

Section: Discussionsupporting

confidence: 67%

Plasmodium berghei Sporozoites Acquire Virulence and Immunogenicity during Mosquito Hemocoel Transit

2014

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bMalaria is a vector-borne disease caused by the single-cell eukaryote Plasmodium. The infectious parasite forms are sporozoites, which originate from midgut-associated oocysts, where they eventually egress and reach the mosquito hemocoel. Sporozoites actively colonize the salivary glands in order to be transmitted to the mammalian host. Whether residence in the salivary glands provides distinct and vital cues for the development of infectivity remains unsolved. In this study, we systematically compared the infectivity of Plasmodium berghei sporozoites isolated from the mosquito hemocoel and salivary glands. Hemocoel sporozoites display a lower proportion of gliding motility but develop into liver stages when added to cultured hepatoma cells or after intravenous injection into mice. Mice infected by hemocoel sporozoites had blood infections similar to those induced by sporozoites liberated from salivary glands. These infected mice display indistinguishable systemic inflammatory cytokine responses and develop experimental cerebral malaria. When used as metabolically active, live attenuated vaccine, hemocoel sporozoites elicit substantial protection against sporozoite challenge infections. Collectively, these findings show that salivary gland colonization does not influence parasite virulence in the mammalian host when sporozoites are administered intravenously. This conclusion has important implications for in vitro sporozoite production and manufacturing of whole-sporozoite vaccines.

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Section: Discussionsupporting

confidence: 67%

Plasmodium berghei Sporozoites Acquire Virulence and Immunogenicity during Mosquito Hemocoel Transit

2014

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“…Presumably, higher expression in P. vivax -infected mosquitoes may contribute to the sporozoites need to mediate stress and thermotolerance when transitioning between hosts during multiple mosquito blood meals. Further, HSP20 has specifically been implemented in regulation of sporozoite adhesion and locomotion 89 . Additionally, we found down-regulation of three salivary gland proteins (ADIR014650, ADIR003224, and ADIR004887) in P. vivax -infected salivary glands previously unreported.…”

Section: Discussionmentioning

confidence: 99%

Unraveling the Plasmodium vivax sporozoite transcriptional journey from mosquito vector to human host

Roth

Adapa

Zhang

et al. 2018

Sci Rep

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Malaria parasites transmitted by mosquito bite are remarkably efficient in establishing human infections. The infection process requires roughly 30 minutes and is highly complex as quiescent sporozoites injected with mosquito saliva must be rapidly activated in the skin, migrate through the body, and infect the liver. This process is poorly understood for Plasmodium vivax due to low infectivity in the in vitro models. To study this skin-to-liver-stage of malaria, we used quantitative bioassays coupled with transcriptomics to evaluate parasite changes linked with mammalian microenvironmental factors. Our in vitro phenotyping and RNA-seq analyses revealed key microenvironmental relationships with distinct biological functions. Most notable, preservation of sporozoite quiescence by exposure to insect-like factors coupled with strategic activation limits untimely activation of invasion-associated genes to dramatically increase hepatocyte invasion rates. We also report the first transcriptomic analysis of the P. vivax sporozoite interaction in salivary glands identifying 118 infection-related differentially-regulated Anopheles dirus genes. These results provide important new insights in malaria parasite biology and identify priority targets for antimalarial therapeutic interventions to block P. vivax infection.

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“…It has been reported that antibodies against HSP20 reduce host-cell invasion by B. divergens , T. gondii and N. caninum [30, 31]. In Plasmodium , deletion of the hsp20 gene results in altered sporozoite speed and substrate adhesion leading to an impaired natural malaria transmission in the host [32, 33]. Although HSP20 is predicted to be synthesized in the cytosol, it localizes to the IMC in T. gondii [28], P. falciparum [32] and to the pellicle in Babesia [34].…”

Section: Introductionmentioning

confidence: 99%

N-terminal palmitoylation is required for Toxoplasma gondii HSP20 inner membrane complex localization

Napoli

Miguel

Lebrun

et al. 2013

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

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Toxoplasma gondii is an obligate intracellular parasite and the causative agent of toxoplasmosis. Protein palmitoylation is known to play roles in signal transduction and in enhancing the hydrophobicity of proteins thus contributing to their membrane association. Global inhibition of protein palmitoylation has been shown to affect T. gondii physiology and invasion of the host cell. However, the proteins affected by this modification have been understudied. This paper shows that the small heat shock protein 20 from T. gondii (TgHSP20) is synthesized as a mature protein in the cytosol and is palmitoylated in three cysteine residues. However, its localization at the inner membrane complex (IMC) is dependent only on N-terminal palmitoylation. Absence or incomplete N-terminal palmitoylation causes TgHSP20 to partially accumulate in a membranous structure. Interestingly, TgHSP20 palmitoylation is not responsible for its interaction with the daughter cells IMCs. Together, our data describe the importance of palmitoylation in protein targeting to the IMC in T. gondii.

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Small heat shock proteins in cellular adhesion and migration

Cited by 12 publications

References 66 publications

Plasmodium berghei Sporozoites Acquire Virulence and Immunogenicity during Mosquito Hemocoel Transit

Plasmodium berghei Sporozoites Acquire Virulence and Immunogenicity during Mosquito Hemocoel Transit

Unraveling the Plasmodium vivax sporozoite transcriptional journey from mosquito vector to human host

N-terminal palmitoylation is required for Toxoplasma gondii HSP20 inner membrane complex localization

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