At the onset of metamorphosis, Drosophila salivary gland cells undergo a burst of
glue granule secretion to attach the forming pupa to a solid surface. Here, we show
that excess granules evading exocytosis are degraded via direct fusion with lysosomes,
a secretory granule-specific autophagic process known as crinophagy. We find that
the tethering complex HOPS (homotypic fusion and protein sorting); the small GTPases
Rab2, Rab7, and its effector, PLEKHM1; and a SNAP receptor complex consisting of Syntaxin
13, Snap29, and Vamp7 are all required for the fusion of secretory granules with lysosomes.
Proper glue degradation within lysosomes also requires the Uvrag-containing Vps34
lipid kinase complex and the v-ATPase proton pump, whereas Atg genes involved in macroautophagy
are dispensable for crinophagy. Our work establishes the molecular mechanism of developmentally
programmed crinophagy in Drosophila and paves the way for analyzing this process in
metazoans.
