title: A Drosophila ortholog of the human MRJ modulates polyglutamine toxicity and aggregation.
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.
authors.affiliation: Department of Physiology and Biophysics, Center for Neuroscience, School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY 14214, USA.
authors.forename: Zahra
authors.initials: Z
authors.lastname: Fayazi
authors.forename: Srimoyee
authors.initials: S
authors.lastname: Ghosh
authors.forename: Susan
authors.initials: S
authors.lastname: Marion
authors.forename: Xiankun
authors.initials: X
authors.lastname: Bao
authors.forename: Marlene
authors.initials: M
authors.lastname: Shero
authors.forename: Parsa
authors.initials: P
authors.lastname: Kazemi-Esfarjani
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D030801:Animals, Genetically Modified; D001483:Base Sequence; D042622:DNA Repeat Expansion / Q000235:genetics; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000196:embryology* / Q000235:genetics / Q000378:metabolism; D005123:Eye / Q000196:embryology* / Q000378:metabolism / Q000503:physiopathology; D005124:Eye Abnormalities / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D050956:HSP40 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D002479:Inclusion Bodies / Q000235:genetics* / Q000378:metabolism; D018832:Molecular Chaperones / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D010455:Peptides / Q000235:genetics* / Q000378:metabolism; D017956:Photoreceptor Cells, Invertebrate / Q000002:abnormalities / Q000378:metabolism / Q000503:physiopathology; D017434:Protein Structure, Tertiary / Q000235:genetics; D050436:Regulatory Elements, Transcriptional / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D012160:Retina / Q000002:abnormalities / Q000378:metabolism / Q000503:physiopathology
chemical_list: C485565:DNAJB6 protein, human; D029721:Drosophila Proteins; D050956:HSP40 Heat-Shock Proteins; D018832:Molecular Chaperones; D009419:Nerve Tissue Proteins; D010455:Peptides; D012097:Repressor Proteins; C516349:mrj protein, Drosophila; C097188:polyglutamine