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Updated: Jul 20, 2026
Monitoring Cell-to-cell Transmission of Prion-like Protein Aggregates in Drosophila Melanogaster
Published on: March 12, 2018
A Drosophila ortholog of the human MRJ modulates polyglutamine toxicity and aggregation
Zahra Fayazi1, Srimoyee Ghosh, Susan Marion
1Department of Physiology and Biophysics, Center for Neuroscience, School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY 14214, USA.
Abstract:
In the Drosophila eye, proteins with an expanded polyglutamine (polyQ) tract form nuclear and cytoplasmic inclusions and produce cytotoxicity, demonstrated as loss of eye pigmentation and structural integrity. An EP P-element that suppressed the loss of eye pigmentation was inserted 9.7 kb upstream of dmrj, a gene that encodes an ortholog of a brain-enriched cochaperone, the human MRJ (mammalian relative of DnaJ). Despite the large distance between them, quantitative polymerase chain reaction indicated that the EP could overexpress dmrj. In the retina and other neurons, transgenic dMRJ suppressed polyQ toxicity and colocalized with its inclusions. In the photoreceptors, expression of another suppressor with a J domain, dHDJ1, but not dMRJ, prior to expression of expanded polyQs dramatically promoted cytoplasmic aggregation. However, both proteins increased the level of detergent-soluble, monomeric polyQ-expanded proteins. These findings exemplify the functional similarities and differences between J domain proteins in suppressing polyQ toxicity.
Insights
Researchers found that dMRJ and dHDJ1 proteins can suppress polyglutamine (polyQ) toxicity in Drosophila. While both increase soluble polyQ proteins, dHDJ1 promotes aggregation, unlike dMRJ.
Area of Science:
- Neuroscience
- Genetics
- Molecular Biology
Background:
- Expanded polyglutamine (polyQ) tracts in proteins cause cytotoxicity and inclusions in Drosophila.
- A P-element insertion upstream of the dmrj gene suppressed polyQ-induced eye pigmentation loss.
Purpose of the Study:
- To investigate the role of dmrj, an ortholog of human MRJ, in suppressing polyQ toxicity.
- To compare the functions of dMRJ and dHDJ1, both J domain proteins, in polyQ toxicity.
Main Methods:
- Quantitative polymerase chain reaction (qPCR) to confirm dmrj overexpression.
- Transgenic expression of dMRJ and dHDJ1 in Drosophila.
- Observation of polyQ toxicity markers (eye pigmentation, structural integrity) and protein aggregation.
Main Results:
- Transgenic dMRJ suppressed polyQ toxicity and colocalized with inclusions in neurons.
- dHDJ1, but not dMRJ, promoted cytoplasmic aggregation when expressed before polyQ proteins.
- Both dMRJ and dHDJ1 increased detergent-soluble, monomeric polyQ-expanded proteins.
Conclusions:
- dMRJ and dHDJ1 exhibit functional similarities and differences in suppressing polyQ toxicity.
- J domain proteins play a complex role in modulating polyQ protein aggregation and toxicity.
