Cologne Seminars on Ageing "Role of late endosomal autophagy-dependent secretion in Parkinson’s disease and glioblastoma"

About Dr. Galli's talk:

Intracellular membrane trafficking is critical for cell function and intercellular communication. Beyond the conventional Golgi-dependent pathway, cells employ unconventional secretion routes, notably via late endosomal and autophagy-dependent mechanisms.
Our research focuses on the SNARE protein VAMP7, a key player in exosome-mediated secretion. We show that VAMP7 is involved in the secretion of misfolded proteins such as α-synuclein and neuropeptides like VGF, a potential Parkinson’s disease biomarker. Notably, the PD-linked kinase LRRK2 interacts with VAMP7 and VAMP4, modulating VGF secretion. In VAMP7 knockout cells, transcriptomic and functional analyses reveal mitochondrial and ER stress, defective mitochondrial-derived vesicle trafficking, and altered secretion of stress-induced components.
In glioblastoma models, VAMP7 deletion leads to larger, more necrotic tumors with increased macrophage infiltration, whereas autophagy-null tumors are smaller. These findings suggest that late endosomal secretion regulates mitochondrial and ER quality control and plays a role in tumor progression.
Overall, our work highlights late endosomal autophagy-dependent secretion as a key stress-response mechanism with implications for neurodegeneration and cancer.