Title :

Secretion of VGF relies on the interplay between LRRK2 and post-Golgi v-SNAREs.

Author(s) :

Filippini, F. [Auteur]
Nola, S. [Auteur]
Zahraoui, A. [Auteur]
Roger, K. [Auteur]
Esmaili, M. [Auteur]
Sun, J. [Auteur]
Wojnacki, J. [Auteur]
Vlieghe, A. [Auteur]
Bun, P. [Auteur]
Blanchon, S. [Auteur]
Rain, J. C. [Auteur]
Taymans, Jean-Marc [Auteur]
Lille Neurosciences & Cognition (LilNCog) - U 1172
Chartier-Harlin, Marie-Christine [Auteur]
Lille Neurosciences & Cognition (LilNCog) - U 1172
Guerrera, C. [Auteur]
Galli, Thierry [Auteur]
Institut de psychiatrie et neurosciences de Paris [IPNP - U1266 Inserm]

Journal title :

Cell Reports

Volume number :

42

Pages :

112221

Publisher :

Cell Press

Publication date :

2023-03-19

ISSN :

2211-1247

HAL domain(s) :

Sciences du Vivant [q-bio]

English abstract : [en]

The neuropeptide VGF was recently proposed as a neurodegeneration biomarker. The Parkinson’s disease-related protein leucine-rich repeat kinase 2 (LRRK2) regulates endolysosomal dynamics, a process that involves SNARE-mediated ...
Show more >The neuropeptide VGF was recently proposed as a neurodegeneration biomarker. The Parkinson’s disease-related protein leucine-rich repeat kinase 2 (LRRK2) regulates endolysosomal dynamics, a process that involves SNARE-mediated membrane fusion and could regulate secretion. Here we investigate potential biochemical and functional links between LRRK2 and v-SNAREs. We find that LRRK2 directly interacts with the v-SNAREs VAMP4 and VAMP7. Secretomics reveals VGF secretory defects in VAMP4 and VAMP7 knockout (KO) neuronal cells. In contrast, VAMP2 KO “regulated secretion-null” and ATG5 KO “autophagy-null” cells release more VGF. VGF is partially associated with extracellular vesicles and LAMP1+ endolysosomes. LRRK2 expression increases VGF perinuclear localization and impairs its secretion. Retention using selective hooks (RUSH) assays show that a pool of VGF traffics through VAMP4+ and VAMP7+ compartments, and LRRK2 expression delays its transport to the cell periphery. Overexpression of LRRK2 or VAMP7-longin domain impairs VGF peripheral localization in primary cultured neurons. Altogether, our results suggest that LRRK2 might regulate VGF secretion via interaction with VAMP4 and VAMP7.Show less >

Language :

Anglais

Audience :

Internationale

Popular science :

Non

Administrative institution(s) :

Université de Lille
Inserm
CHU Lille

Collections :

• Lille Neurosciences & Cognition (LilNCog) - U 1172

Submission date :

2024-01-15T23:26:52Z
2024-10-16T07:00:40Z