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Citation
Park, D., Hadžić, T., Yin, P., Rusch, J., Abruzzi, K., Rosbash, M., Skeath, J.B., Panda, S., Sweedler, J.V., Taghert, P.H. (2011). Molecular organization of Drosophila neuroendocrine cells by dimmed.  Curr. Biol. 21(18): 1515--1524.
FlyBase ID
FBrf0216231
Publication Type
Research paper
Abstract

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.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.The results provide a rigorous molecular framework with which to describe the fundamental regulatory organization of diverse neuroendocrine cells.

Graphical Abstract
Obtained with permission from Cell Press.
PubMed ID
PubMed Central ID
PMC3184372 (PMC) (EuropePMC)
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    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    Curr. Biol.
    Title
    Current Biology
    Publication Year
    1991-
    ISBN/ISSN
    0960-9822
    Data From Reference