Dr Thierry Galli - Université Paris Cité: "Role of unconventional secretory autophagy in the brain - potential role in Parkinson's and glioblastoma"

Speaker:

Dr Thierry Galli
Université Paris Cité
Paris, France

Title: Role of unconventional secretory autophagy in the brain - potential role in Parkinson's and glioblastoma

Abstract: 

Communication between cells, in the brain, is important for proper development and function. Conventional secretion which is ER-Golgi mediated relies on secretory vesicles. In the brain, conventional secretion refers to synaptic vesicle and secretory granule mediated release of classical neurotransmitters and neuropeptides. However, the molecules released by the vesicular late-endosome mediated unconventional secretion in the brain and their effects are largely unidentified. Recent work by our lab has characterized a new secretory autophagy-dependent pathway which relies on VAMP7, a tetanus neurotoxin insensitive vesicular SNARE. We found that endoplasmic reticulum and mitochondrial elements can be incorporated into late endosomes and can later be released by this secretory mechanism. This process is more efficient in the absence of degradative autophagy. We have recently uncovered potential function of this secretion in the communication between neuronal cells and glioma cells. Additionnally, we identified a biochemical and functional link between VAMP7 and Leucine Rich Repeat Kinase 2 (LRRK2). LRRK2 is associated with Parkinson’s disease and was suggested to regulate endolysosomal dynamics. We found that VAMP7-KO neuron-like cells secreted less pro-VGF a biomarker of Parkinson’s and other neurodegenerative diseases. The pathogenic R1441C mutant of LRRK2 affected the subcellular localization of VGF and LRRK2 expression inhibited the secretion of pro-VGF. These results further suggest the importance of VAMP7-dependent unconventional secretion of pro-VGF in neurodegeneration.

Further reading

1. Vats, S., and Galli, T. (2021). Introducing secretory reticulophagy/ER-phagy (SERP), a VAMP7-dependent pathway involved in neurite growth. Autophagy 17, 1037–1039.

2. Vats, S., and Galli, T. (2022). Role of SNAREs in Unconventional Secretion-Focus on the VAMP7-Dependent Secretion. Front. Cell Dev. Biol. 10, 884020.

3. Wojnacki, J., Nola, S., Bun, P., Cholley, B., Filippini, F., Pressé, M. T., Lipecka, J., Man Lam, S., N’guyen, J., Simon, A., et al. (2020). Role of VAMP7-Dependent Secretion of Reticulon 3 in Neurite Growth. Cell Rep. 33, 108536.

4. Wang, G., Nola, S., Bovio, S., Bun, P., Coppey-Moisan, M., Lafont, F., and Galli, T. (2018). Biomechanical Control of Lysosomal Secretion Via the VAMP7 Hub: A Tug-of-War between VARP and LRRK1. iScience 4, 127–143.