PT  - JOURNAL ARTICLE
AU  - Dongkook Park
AU  - Peiyao Li
AU  - Adish Dani
AU  - Paul H. Taghert
TI  - Peptidergic Cell-Specific Synaptotagmins in <em>Drosophila</em>: Localization to Dense-Core Granules and Regulation by the bHLH Protein DIMMED
AID  - 10.1523/JNEUROSCI.2075-14.2014
DP  - 2014 Sep 24
TA  - The Journal of Neuroscience
PG  - 13195--13207
VI  - 34
IP  - 39
4099  - http://www.jneurosci.org/content/34/39/13195.short
4100  - http://www.jneurosci.org/content/34/39/13195.full
SO  - J. Neurosci.2014 Sep 24; 34
AB  - Bioactive peptides are packaged in large dense-core secretory vesicles, which mediate regulated secretion by exocytosis. In a variety of tissues, the regulated release of neurotransmitters and hormones is dependent on calcium levels and controlled by vesicle-associated synaptotagmin (SYT) proteins. Drosophila express seven SYT isoforms, of which two (SYT-α and SYT-β) were previously found to be enriched in neuroendocrine cells. Here we show that SYT-α and SYT-β tissue expression patterns are similar, though not identical. Furthermore, both display significant overlap with the bHLH transcription factor DIMM, a known neuroendocrine (NE) regulator. RNAi-mediated knockdown indicates that both SYT-α and SYT-β functions are essential in identified NE cells as these manipulations phenocopy loss-of-function states for the indicated peptide hormones. In Drosophila cell culture, both SYT-α and neuropeptide cargo form DIMM-dependent fluorescent puncta that are coassociated by super-resolution microscopy. DIMM is required to maintain SYT-α and SYT-β protein levels in DIMM-expressing cells in vivo. In neurons normally lacking all three proteins (DIMM−/SYT-α−/SYT-β−), DIMM misexpression conferred accumulation of endogenous SYT-α and SYT-β proteins. Furthermore transgenic SYT-α does not appreciably accumulate in nonpeptidergic neurons in vivo but does so if DIMM is comisexpressed. Among Drosophila syt genes, only syt-α and syt-β RNA levels are upregulated by DIMM overexpression. Together, these data suggest that SYT-α and SYT-β are important for NE cell physiology, that one or both are integral membrane components of the large dense-core vesicles, and that they are closely regulated by DIMM at a post-transcriptional level.