Transcriptional Orchestration of the Regulated Secretory Pathway in Neurons by the bHLH protein DIMM

Yoshitaka Hamanaka, Dongkook Park, Ping Yin, Suresh P. Annangudi, Tara N. Edwards, Jonathan V Sweedler, Ian A. Meinertzhagen, Paul H. Taghert

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)9-18
Number of pages10
JournalCurrent Biology
Volume20
Issue number1
DOIs
StatePublished - Jan 12 2010

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Keywords

  • MOLNEURO

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Hamanaka, Y., Park, D., Yin, P., Annangudi, S. P., Edwards, T. N., Sweedler, J. V., Meinertzhagen, I. A., & Taghert, P. H. (2010). Transcriptional Orchestration of the Regulated Secretory Pathway in Neurons by the bHLH protein DIMM. Current Biology, 20(1), 9-18. https://doi.org/10.1016/j.cub.2009.11.065