A Drosophila ortholog of the human MRJ modulates polyglutamine toxicity and aggregation

Fayazi, Zahra; Ghosh, Srimoyee; Marion, Susan; Bao, Xiankun; Shero, Marlene; Kazemi-Esfarjani, Parsa

doi:10.1016/j.nbd.2006.06.015

Cited by 44 publications

(40 citation statements)

References 105 publications

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“…Therefore, we tested which of the Drosophila small HSPs could suppress aggregation of an EGFP‐tagged huntingtin exon‐1 containing 119 glutamines (EGFP‐HDQ119) in S2 cells. The Dm ortholog of the human DNAJB6, MRJ, previously identified in a screen for suppressors of polyglutamine (polyQ) toxicity (Fayazi et al ., 2006; Hageman et al ., 2010) was used as a positive control and indeed completely inhibited aggregate formation in S2 cells as demonstrated using filter trap binding (Fig. 4A).…”

Section: Resultsmentioning

confidence: 99%

“…(A) EGFP ‐Htt‐Q119, harboring exon 1 fragment of the huntingtin protein containing 119 glutamine repeats, was coexpressed in Schneider's S2 cells together with an empty vector (control) or the various D. melanogaster small HSP s. MRJ , a well‐known potent inhibitor of polyQ aggregation (Chuang et al ., 2002; Fayazi et al ., 2006), was included as a positive control. Forty‐eight hours after transfection, S2 cells were lysed and analyzed using the filter trap assay.…”

Section: Resultsmentioning

confidence: 99%

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Specific protein homeostatic functions of small heat‐shock proteins increase lifespan

et al. 2015

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SummaryDuring aging, oxidized, misfolded, and aggregated proteins accumulate in cells, while the capacity to deal with protein damage declines severely. To cope with the toxicity of damaged proteins, cells rely on protein quality control networks, in particular proteins belonging to the family of heat‐shock proteins (HSPs). As safeguards of the cellular proteome, HSPs assist in protein folding and prevent accumulation of damaged, misfolded proteins. Here, we compared the capacity of all Drosophila melanogaster small HSP family members for their ability to assist in refolding stress‐denatured substrates and/or to prevent aggregation of disease‐associated misfolded proteins. We identified CG14207 as a novel and potent small HSP member that exclusively assisted in HSP70‐dependent refolding of stress‐denatured proteins. Furthermore, we report that HSP67BC, which has no role in protein refolding, was the most effective small HSP preventing toxic protein aggregation in an HSP70‐independent manner. Importantly, overexpression of both CG14207 and HSP67BC in Drosophila leads to a mild increase in lifespan, demonstrating that increased levels of functionally diverse small HSPs can promote longevity in vivo.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Specific protein homeostatic functions of small heat‐shock proteins increase lifespan

et al. 2015

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“…However, we did not observe intermediate filament protein aggregates, similar to those seen in Mrj À/À trophoblast cells (Watson et al, 2007), in Mrj À/À neural tubes. Notably, other studies have shown that Mrj associates with neural disease-related protein aggregates, for example, polyglutamine-expanded Huntington's disease protein (Chuang et al, 2002;Fayazi et al, 2006) and Lewy bodies of Parkinson's disease (Durrenberger et al, 2009). This suggests that Mrj may prevent the aggregation of these and/or other unknown proteins that would lead to abnormal neural tube closure.…”

Section: Discussionmentioning

confidence: 99%

Neural stem cell self‐renewal requires the Mrj co‐chaperone

Watson

Mattar

Schuurmans

et al. 2009

Developmental Dynamics

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The Mrj co-chaperone is expressed throughout the mouse conceptus, yet its requirement for placental development has prohibited a full understanding of its embryonic function. Here, we show that Mrj 2/2 embryos exhibit neural tube defects independent of the placenta phenotype, including exencephaly and thin-walled neural tubes. Molecular analyses revealed fewer proliferating cells and a down-regulation of early neural progenitor (Pax6, Olig2, Hes5) and neuronal (Nscl2, SCG10) cell markers in Mrj

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“…In transgenic Drosophila model of the Huntington disease, the retinal degeneration occurs relatively fast when the polyQ is expressed during neuronal differentiation (3rd instar larvae), and takes several weeks if expressed when eye is in an advanced stage of development (Fayazi et al, 2006). Thus, developing cells appeared to be more susceptible to polyQ.…”

Section: Discussionmentioning

confidence: 99%

ORMOSIL nanoparticles as a non-viral gene delivery vector for modeling polyglutamine induced brain pathology

Klejbor

Stachowiak

Bharali

et al. 2007

Journal of Neuroscience Methods

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A Drosophila ortholog of the human MRJ modulates polyglutamine toxicity and aggregation

Cited by 44 publications

References 105 publications

Specific protein homeostatic functions of small heat‐shock proteins increase lifespan

Specific protein homeostatic functions of small heat‐shock proteins increase lifespan

Neural stem cell self‐renewal requires the Mrj co‐chaperone

ORMOSIL nanoparticles as a non-viral gene delivery vector for modeling polyglutamine induced brain pathology

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