Molecular organization of drosophila neuroendocrine cells by dimmed

Dongkook Park, Tarik Hadžić, Ping Yin, Jannette Rusch, Katharine Abruzzi, Michael Rosbash, James B. Skeath, Satchidananda Panda, Jonathan V. Sweedler, Paul H. Taghert

Research output: Contribution to journalArticle

Abstract

Background: In Drosophila, the basic-helix-loop-helix protein DIMM coordinates the molecular and cellular properties of all major neuroendocrine cells, irrespective of the secretory peptides they produce. When expressed by nonneuroendocrine neurons, DIMM confers the major properties of the regulated secretory pathway and converts such cells away from fast neurotransmission and toward a neuroendocrine state. Results: We first identified 134 transcripts upregulated by DIMM in embryos and then evaluated them systematically using diverse assays (including embryo in situ hybridization, in vivo chromatin immunoprecipitation, and cell-based transactivation assays). We conclude that of eleven strong candidates, six are strongly and directly controlled by DIMM in vivo. The six targets include several large dense-core vesicle (LDCV) proteins, but also proteins in non-LDCV compartments such as the RNA-associated protein Maelstrom. In addition, a functional in vivo assay, combining transgenic RNA interference with MS-based peptidomics, revealed that three DIMM targets are especially critical for its action. These include two well-established LDCV proteins, the amidation enzyme PHM and the ascorbate-regenerating electron transporter cytochrome b 561-1. The third key DIMM target, CAT-4 (CG13248), has not previously been associated with peptide neurosecretion - it encodes a putative cationic amino acid transporter, closely related to the Slimfast arginine transporter. Finally, we compared transcripts upregulated by DIMM with those normally enriched in DIMM neurons of the adult brain and found an intersection of 18 DIMM-regulated genes, which included all six direct DIMM targets. Conclusions: The results provide a rigorous molecular framework with which to describe the fundamental regulatory organization of diverse neuroendocrine cells.

Original languageEnglish (US)
Pages (from-to)1515-1524
Number of pages10
JournalCurrent Biology
Volume21
Issue number18
DOIs
StatePublished - Sep 27 2011

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Neuroendocrine Cells
Drosophila
Secretory Vesicles
Assays
Proteins
proteins
Neurons
cells
transporters
Basic Amino Acid Transport Systems
embryo (animal)
assays
Embryonic Structures
neurons
Neurosecretion
peptides
RNA
neurosecretion
amino acid transporters
Peptides

ASJC Scopus subject areas

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

Cite this

Park, D., Hadžić, T., Yin, P., Rusch, J., Abruzzi, K., Rosbash, M., ... Taghert, P. H. (2011). Molecular organization of drosophila neuroendocrine cells by dimmed. Current Biology, 21(18), 1515-1524. https://doi.org/10.1016/j.cub.2011.08.015

Molecular organization of drosophila neuroendocrine cells by dimmed. / Park, Dongkook; Hadžić, Tarik; Yin, Ping; Rusch, Jannette; Abruzzi, Katharine; Rosbash, Michael; Skeath, James B.; Panda, Satchidananda; Sweedler, Jonathan V.; Taghert, Paul H.

In: Current Biology, Vol. 21, No. 18, 27.09.2011, p. 1515-1524.

Research output: Contribution to journalArticle

Park, D, Hadžić, T, Yin, P, Rusch, J, Abruzzi, K, Rosbash, M, Skeath, JB, Panda, S, Sweedler, JV & Taghert, PH 2011, 'Molecular organization of drosophila neuroendocrine cells by dimmed', Current Biology, vol. 21, no. 18, pp. 1515-1524. https://doi.org/10.1016/j.cub.2011.08.015
Park D, Hadžić T, Yin P, Rusch J, Abruzzi K, Rosbash M et al. Molecular organization of drosophila neuroendocrine cells by dimmed. Current Biology. 2011 Sep 27;21(18):1515-1524. https://doi.org/10.1016/j.cub.2011.08.015
Park, Dongkook ; Hadžić, Tarik ; Yin, Ping ; Rusch, Jannette ; Abruzzi, Katharine ; Rosbash, Michael ; Skeath, James B. ; Panda, Satchidananda ; Sweedler, Jonathan V. ; Taghert, Paul H. / Molecular organization of drosophila neuroendocrine cells by dimmed. In: Current Biology. 2011 ; Vol. 21, No. 18. pp. 1515-1524.
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