title: Molecular organization of Drosophila neuroendocrine cells by Dimmed.
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.
authors: Department of Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors: Dongkook
authors: D
authors: Park
authors: Tarik
authors: T
authors: Hadžić
authors: Ping
authors: P
authors: Yin
authors: Jannette
authors: J
authors: Rusch
authors: Katharine
authors: K
authors: Abruzzi
authors: Michael
authors: M
authors: Rosbash
authors: James B
authors: JB
authors: Skeath
authors: Satchidananda
authors: S
authors: Panda
authors: Jonathan V
authors: JV
authors: Sweedler
authors: Paul H
authors: PH
authors: Taghert
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D004330:Drosophila / Q000166:cytology* / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D004625:Embryo, Nonmammalian / Q000378:metabolism; D005786:Gene Expression Regulation; D017403:In Situ Hybridization; D008969:Molecular Sequence Data; D055099:Neuroendocrine Cells / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D029721:Drosophila Proteins; D012333:RNA, Messenger; C491313:dimm protein, Drosophila