Ecdysone receptor isoform specific regulation of secretory granule acidification in the larval Drosophila salivary gland

Bulk production and release of glue containing secretory granules takes place in the larval salivary gland during Drosophila development in order to attach the metamorphosing animal to a dry surface. These granules undergo a maturation process to prepare glue for exocytosis, which includes homotypic fusions to increase the size of granules, vesicle acidification and ion uptake. The steroid hormone 20-hydroxyecdysone is known to be required for the first and last steps of this process: glue synthesis and secretion, respectively. Here we show that the B1 isoform of Ecdysone receptor (EcR), together with its binding partner Ultraspiracle, are also necessary for the maturation of glue granules by promoting their acidification via regulation of Vha55 expression, which encodes an essential subunit of the V-ATPase proton pump. This is antagonized by the EcR-A isoform, overexpression of which decreases EcR-B1 and Vha55 expression and glue granule acidification. Our data shed light on a previously unknown, ecdysone receptor isoform-specific regulation of glue granule maturation.