title: Expression of polyQ aggregates in Malpighian tubules leads to degeneration in Drosophila melanogaster.
abstract: BACKGROUND
  Polyglutamine (polyQ) disorders are caused by expanded CAG (Glutamine) repeats in neurons in the brain. The expanded repeats are also expressed in the non-neuronal cells, however, their contribution to disease pathogenesis is not very well studied. In the present study, we have expressed a stretch of 127 Glutamine repeats in Malpighian tubules (MTs) of Drosophila melanogaster as these tissues do not undergo ecdysone induced histolysis during larval to pupal transition at metamorphosis.
  
  
  RESULTS
  Progressive degeneration, which is the hallmark of neurodegeneration is also observed in MTs. The mutant protein forms inclusion bodies in the nucleus resulting in expansion of the nucleus and affect chromatin organization which appear loose and open, eventually resulting in DNA fragmentation and blebbing. A virtual absence of tubule lumen was observed followed by functional abnormalities. As development progressed, severe abnormalities affecting pupal epithelial morphogenesis processes were observed resulting in complete lethality. Distribution of heterogeneous RNA binding protein (hnRNP), HRB87F, Wnt/wingless and JNK signaling and expression of Relish was also found to be affected. Expression of resistance genes following polyQ expression was up regulated.
  
  
  CONCLUSIONS
  The present study gives an insight into the effects of polyQ aggregates in non-neuronal tissues.
authors.affiliation: Cytogenetics Laboratory, Department of Zoology, Banaras Hindu University, Varanasi 221005, Uttar Pradesh, India.
authors.forename: Suman
authors.initials: S
authors.lastname: Yadav
authors.affiliation: Cytogenetics Laboratory, Department of Zoology, Banaras Hindu University, Varanasi 221005, Uttar Pradesh, India. Electronic address: madhu@bhu.ac.in.
authors.forename: Madhu G
authors.initials: MG
authors.lastname: Tapadia
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D000818:Animals; D015820:Cadherins / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D002843:Chromatin / Q000378:metabolism; D029721:Drosophila Proteins / Q000378:metabolism; D004331:Drosophila melanogaster / Q000196:embryology* / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D017344:Genes, Insect; D034441:Heterogeneous-Nuclear Ribonucleoproteins / Q000378:metabolism; D002479:Inclusion Bodies / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008317:Malpighian Tubules / Q000196:embryology* / Q000473:pathology*; D010455:Peptides / Q000378:metabolism*; D010766:Phosphorylation; D066329:Protein Aggregates; D011679:Pupa / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D060449:Wnt Signaling Pathway
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D015820:Cadherins; D002843:Chromatin; D029721:Drosophila Proteins; D034441:Heterogeneous-Nuclear Ribonucleoproteins; D010455:Peptides; D066329:Protein Aggregates; D012333:RNA, Messenger; C097188:polyglutamine; D048031:JNK Mitogen-Activated Protein Kinases