Transcriptional orchestration of the regulated secretory pathway in neurons by the bHLH protein DIMM.
BACKGROUND
The Drosophila basic helix-loop-helix (bHLH) gene dimmed (dimm) promotes a neurosecretory/neuroendocrine phenotype in cells but is not associated with specific neuropeptides or neurohormones. Rather, it is expressed by those peptidergic neurons that project long axons and appear to produce large amounts of secretory peptides. Here, we genetically transform nonpeptidergic neurons in Drosophila to study DIMM's action mechanisms.


RESULTS
Nonpeptidergic neurons normally fail to accumulate ectopic neuropeptides. We now show that they will do so when they are also forced to express ectopic DIMM. Furthermore, mass spectrometry shows that photoreceptors, which are normally nonpeptidergic, fail to process an ectopic neuropeptide precursor to make bioactive peptides but will do so efficiently when DIMM is co-misexpressed. Likewise, photoreceptors, which normally package the fast neurotransmitter histamine within small clear synaptic vesicles, produce numerous large dense-core vesicles (LDCVs) when they misexpress DIMM. These novel LDCVs accumulate ectopic neuropeptide when photoreceptors co-misexpress a neuropeptide transgene. DIMM-expressing photoreceptors no longer accumulate histamine and lose synaptic organelles critical to their normal physiology.


CONCLUSIONS
These findings indicate that DIMM suppresses conventional fast neurotransmission and promotes peptidergic neurosecretory properties. We conclude that DIMM normally provides a comprehensive transcriptional control to direct the differentiation of dedicated neuroendocrine neurons.
Hamanaka
Yoshitaka
Y
Department of Psychology, Life Sciences Centre, Dalhousie University, Halifax, NS B3H 4J1, Canada.
Park
Dongkook
D
Yin
Ping
P
Annangudi
Suresh P
SP
Edwards
Tara N
TN
Sweedler
Jonathan
J
Meinertzhagen
Ian A
IA
Taghert
Paul H
PH
D000818:Animals; D030801:Animals, Genetically Modified; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics* / Q000502:physiology*; D004330:Drosophila / Q000235:genetics* / Q000502:physiology* / Q000648:ultrastructure; D029721:Drosophila Proteins / Q000235:genetics* / Q000502:physiology*; D019835:FMRFamide / Q000235:genetics / Q000502:physiology; D017344:Genes, Insect; D046529:Microscopy, Electron, Transmission; D009474:Neurons / Q000502:physiology; D009479:Neuropeptides / Q000235:genetics / Q000502:physiology; D017956:Photoreceptor Cells, Invertebrate / Q000502:physiology / Q000648:ultrastructure; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic
D051792:Basic Helix-Loop-Helix Proteins; D029721:Drosophila Proteins; D019835:FMRFamide; D009479:Neuropeptides; D011994:Recombinant Proteins; C491313:dimm protein, Drosophila; C113883:pdf protein, Drosophila