title: Gene expression analysis of Drosophilaa Manf mutants reveals perturbations in membrane traffic and major metabolic changes.
abstract: BACKGROUND
  MANF and CDNF are evolutionarily conserved neurotrophic factors that specifically support dopaminergic neurons. To date, the receptors and signalling pathways of this novel MANF/CDNF family have remained unknown. Independent studies have showed upregulation of MANF by unfolded protein response (UPR). To enlighten the role of MANF in multicellular organism development we carried out a microarray-based analysis of the transcriptional changes induced by the loss and overexpression of Drosophila Manf.
  
  
  RESULTS
  The most dramatic change of expression was observed with genes coding membrane transport proteins and genes related to metabolism. When evaluating in parallel the ultrastructural data and transcriptome changes of maternal/zygotic and only zygotic Manf mutants, the endoplasmic reticulum (ER) stress and membrane traffic alterations were evident. In Drosophila Manf mutants the expression of several genes involved in Parkinson's disease (PD) was altered as well.
  
  
  CONCLUSIONS
  We conclude that besides a neurotrophic factor, Manf is an important cellular survival factor needed to overcome the UPR especially in tissues with high secretory function. In the absence of Manf, the expression of genes involved in membrane transport, particularly exocytosis and endosomal recycling pathway was altered. In neurodegenerative diseases, such as PD, correct protein folding and proteasome function as well as neurotransmitter synthesis and uptake are crucial for the survival of neurons. The degeneration of dopaminergic neurons is the hallmark for PD and our work provides a clue on the mechanisms by which the novel neurotrophic factor MANF protects these neurons.
authors.affiliation: Department of Biosciences, University of Helsinki, Finland. mari.palgi@helsinki.fi
authors.forename: Mari
authors.initials: M
authors.lastname: Palgi
authors.forename: Dario
authors.initials: D
authors.lastname: Greco
authors.forename: Riitta
authors.initials: R
authors.lastname: Lindström
authors.forename: Petri
authors.initials: P
authors.lastname: Auvinen
authors.forename: Tapio I
authors.initials: TI
authors.lastname: Heino
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001692:Biological Transport / Q000235:genetics; D050260:Carbohydrate Metabolism / Q000235:genetics; D002453:Cell Cycle / Q000235:genetics; D016923:Cell Death / Q000235:genetics; D002462:Cell Membrane / Q000378:metabolism*; D004247:DNA / Q000096:biosynthesis / Q000378:metabolism; D004298:Dopamine / Q000096:biosynthesis; D004330:Drosophila / Q000166:cytology / Q000196:embryology / Q000235:genetics* / Q000378:metabolism*; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism; D004625:Embryo, Nonmammalian / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000235:genetics / Q000378:metabolism; D005089:Exocytosis / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling; D006867:Hydrolases / Q000378:metabolism; D040582:Inheritance Patterns / Q000235:genetics; D007814:Larva / Q000166:cytology / Q000201:enzymology / Q000235:genetics / Q000378:metabolism; D008247:Lysosomes / Q000235:genetics; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D009414:Nerve Growth Factors / Q000235:genetics* / Q000378:metabolism; D017510:Protein Folding; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013312:Stress, Physiological / Q000235:genetics; D056811:Unfolded Protein Response / Q000235:genetics
chemical_list: D029721:Drosophila Proteins; C539344:MANF protein, Drosophila; D026901:Membrane Transport Proteins; D009414:Nerve Growth Factors; D012333:RNA, Messenger; D000255:Adenosine Triphosphate; D004247:DNA; D006867:Hydrolases; D004298:Dopamine