Molecular mechanisms of developmentally programmed crinophagy in Drosophila

• Published in: The Journal of cell biology Vol. 217; no. 1; pp. 361 - 374
• Main Authors: Csizmadia, Tamás, Lőrincz, Péter, Hegedűs, Krisztina, Széplaki, Szilvia, Lőw, Péter, Juhász, Gábor
• Format: Journal Article
• Language: English
• Published: United States Rockefeller University Press 02.01.2018; The Rockefeller University Press
• Subjects: Adaptor Proteins, Signal Transducing - genetics; Adenosine triphosphatase; Animals; Autophagy; Autophagy - physiology; Cells; Cells, Cultured; Class III Phosphatidylinositol 3-Kinases - genetics; Drosophila; Drosophila melanogaster - embryology; Drosophila Proteins - genetics; Exocytosis; Fusion protein; Genes; Glue Proteins, Drosophila - genetics; Glue Proteins, Drosophila - metabolism; Granular materials; H+-transporting ATPase; Insects; Lipid kinase; Lipids; Lysosomes; Lysosomes - metabolism; Membrane Fusion - physiology; Metamorphosis; Molecular modelling; Protein transport; Proteins; Pupae; Qa-SNARE Proteins - genetics; R-SNARE Proteins - genetics; rab GTP-Binding Proteins - genetics; rab2 GTP-Binding Protein - genetics; Salivary gland; Secretion; Secretory vesicles; Secretory Vesicles - metabolism; SNARE Proteins - genetics; Syntaxin; Tethering
• ISSN: 0021-9525; 1540-8140
• DOI: 10.1083/jcb.201702145

At the onset of metamorphosis, 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 and paves the way for analyzing this process in metazoans.