Evidence that DmMANF is an invertebrate neurotrophic factor supporting dopaminergic neurons.
In vertebrates the development and function of the nervous system is regulated by neurotrophic factors (NTFs). Despite extensive searches no neurotrophic factors have been found in invertebrates. However, cell ablation studies in Drosophila suggest trophic interaction between neurons and glia. Here we report the invertebrate neurotrophic factor in Drosophila, DmMANF, homologous to mammalian MANF and CDNF. DmMANF is expressed in glia and essential for maintenance of dopamine positive neurites and dopamine levels. The abolishment of both maternal and zygotic DmMANF leads to the degeneration of axonal bundles in the embryonic central nervous system and subsequent nonapoptotic cell death. The rescue experiments confirm DmMANF as a functional ortholog of the human MANF gene thus opening the window for comparative studies of this protein family with potential for the treatment of Parkinson's disease.
Palgi
Mari
M
Institute of Biotechnology, University of Helsinki, 00014, Helsinki, Finland.
Lindström
Riitta
R
Peränen
Johan
J
Piepponen
T Petteri
TP
Saarma
Mart
M
Heino
Tapio I
TI
D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D030801:Animals, Genetically Modified; D004298:Dopamine / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics / Q000502:physiology*; D004331:Drosophila melanogaster; D006801:Humans; D008954:Models, Biological; D008969:Molecular Sequence Data; D009414:Nerve Growth Factors / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000378:metabolism; D016501:Neurites / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D010300:Parkinson Disease / Q000628:therapy; D017386:Sequence Homology, Amino Acid
D029721:Drosophila Proteins; C539344:MANF protein, Drosophila; C099695:MANF protein, human; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D004298:Dopamine