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

被引:46
作者
Hamanaka, Yoshitaka [1 ]
Park, Dongkook [2 ]
Yin, Ping [3 ]
Annangudi, Suresh P. [3 ]
Edwards, Tara N. [1 ]
Sweedler, Jonathan [3 ]
Meinertzhagen, Ian A. [1 ]
Taghert, Paul H. [2 ]
机构
[1] Dalhousie Univ, Dept Psychol, Life Sci Ctr, Halifax, NS B3H 4J1, Canada
[2] Washington Univ, Sch Med, Dept Anat & Neurobiol, St Louis, MO 63110 USA
[3] Univ Illinois, Dept Chem, Urbana, IL 61801 USA
基金
美国国家卫生研究院;
关键词
GRANULE BIOGENESIS; ECTOPIC EXPRESSION; EXOCRINE PANCREAS; CHROMOGRANIN-A; ON/OFF SWITCH; BLOW FLY; DROSOPHILA; NEUROPEPTIDE; GENE; CELLS;
D O I
10.1016/j.cub.2009.11.065
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 mis-express 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.
引用
收藏
页码:9 / 18
页数:10
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