Regulation of Dense-Core Granule Replenishment by Autocrine BMP Signalling in Drosophila Secondary Cells

Abstract

Regulated secretion by glands and neurons involves release of signalling molecules and enzymes selectively concentrated in dense-core granules (DCGs). Although we understand how many secretagogues stimulate DCG release, how DCG biogenesis is then accelerated to replenish the DCG pool remains poorly characterised. Here we demonstrate that each prostate-like secondary cell (SC) in the paired adult Drosophila melanogaster male accessory glands contains approximately ten large DCGs, which are loaded with the Bone Morphogenetic Protein (BMP) ligand Decapentaplegic (Dpp). These DCGs can be marked in living tissue by a glycophosphatidylinositol (GPI) lipid-anchored form of GFP. In virgin males, BMP signalling is sporadically activated by constitutive DCG secretion. Upon mating, approximately four DCGs are typically released immediately, increasing BMP signalling, primarily via an autocrine mechanism. Using inducible knockdown specifically in adult SCs, we show that secretion requires the Soluble NSF Attachment Protein, SNAP24. Furthermore, mating-dependent BMP signalling not only promotes cell growth, but is also necessary to accelerate biogenesis of new DCGs, restoring DCG number within 24 h. Our analysis therefore reveals an autocrine BMP-mediated feedback mechanism for matching DCG release to replenishment as secretion rates fluctuate, and might explain why in other disease-relevant systems, like pancreatic β-cells, BMP signalling is also implicated in the control of secretion.

Rab‐mediated trafficking in the secondary cells of Drosophila male accessory glands and its role in fecundity

“…Consistent with this observation, the genetic reduction of Rab6 prevents the formation of all VLC classes. In contrast, the absence of Rab7 and 11, but not Rab19, results in the loss of only some VLC populations. These losses, however, are sufficient to result in defective female PMR behaviors.…”

“…This resource provides annotations based on a defined vocabulary for each Rab protein expressed in AGs and allows 3D localization tracking down to subcellular resolutions. Thus, our work maps out the maturation of the membrane/protein transport machinery in the AGs over time and adds valuable knowledge to the existing model describing the SC secretion system …”

“…The VLCs are membrane‐bound organelles containing a large internal space. The SCs, like the MCs, are in direct contact with the glandular lumen and are able to contribute to the seminal fluid . Recent findings show that the SCs, however, are not crucial for initiating PMR behaviors.…”

“…Recent findings show that the SCs, however, are not crucial for initiating PMR behaviors. Instead, through genetic manipulations that affect SCs and/or their VLCs, SCs have been shown to play a critical role in sustaining the female PMR for up to 10 days after mating . Given their prominence in SC architecture, the biological function of VLCs seems to be key to understanding how SCs function in sustaining the PMR.…”

Nutrient conditions sensed by the reproductive organ during development optimize male fecundity in Drosophila

“…Each of the two lobes of the accessory gland is composed of two types of binucleated cells: approximately 1,000 main cells and 40-60 secondary cells (SCs). SCs have unusually large vacuoles, which are nonacidic secretory vacuoles (SVs) and acidic mature late endosomal multivesicular bodies or lysosomes (MVBLs) (Redhai et al, 2016;Rylett, Walker, Howell, Shirras, & Isaac, 2007). The transcription factors, Defective proventriculus (Dve) and Abdominal-B (Abd-B), are strongly expressed in adult SCs; these transcription factors are essential for male fecundity (Gligorov, Sitnik, Maeda, Wolfner, & Karch, 2013;Minami et al, 2012).…”