HUN-REN Szegedi Biológiai Kutatóközpont 
2026. jún. 19. | News
Gábor Juhász’s research group previously developed a test system enabling the functional study of crinophagy in a popular model organism, Drosophila. The salivary gland produces a large amount of glue proteins at the end of the larval stage, which is used at the onset of metamorphosis: it mediates the adhesion of the pupa to a solid surface. Importantly, the residual, non-released glue is degraded. The researchers identified the factors involved in the fusion of secretory granules with lysosomes 8 years ago. However, the molecular signal determining whether a secretory granule is directed toward lysosomal degradation rather than secretion remained elusive.
Ubiquitination is the best-known post-translational modification that marks target proteins and organelles for proteasomal or autophagic-lysosomal degradation. In their latest publication, in collaboration with colleagues from Eötvös University, they demonstrated that ubiquitin also marks secretory granules for degradation and identified the ubiquitinating enzyme required for this process (Cnot1). In the absence of Cnot1, ubiquitination and granule degradation are inhibited, whereas overexpression of Cnot1 can induce this process.
These findings are significant because dysregulation of crinophagy may play a role in numerous diseases. For example, if secretory granules that carry inactive digestive enzymes produced by the pancreas are prematurely activated within lysosomes, this can cause severe inflammation. Thus, abnormal crinophagy may contribute to the development of acute pancreatitis. Understanding the molecular basis of this process may therefore enable the development of new treatments.
Salivary gland cells of the fruit fly 2 hours before puparium formationn (A, B) and at the time of pupariation (C, D). Panel A depicts normal cells: secretory granules are shown in magenta, ubiquitin in green, and the nucleus in blue. The magnified detail clearly shows that ubiquitin is bound to the membranes of the secretory granules (yellow arrows). In contrast, this labeling is absent in Panel B, where Cnot4 function was inhibited,. Panels C and D assay acidification of the secretory granules, a phenomenon accompanying crinophagic degradation. In normal cells (C), the granules acidify due to lysosomal fusions that causes quenching of the green signal (GFP), leaving only the magenta signal. In the absence of Cnot4 (D), this process does not occur: many undegraded granules remain in the cells, displaying both green and magenta signals simultaneously.