Endophilin-B regulates autophagy during synapse development and neurodegeneration

Sergio Hernandez-Diaz, Saurav Ghimire, Irene Sanchez-Mirasierra, Carla Montecinos-Oliva, Jef Swerts, Sabine Kuenen, Patrik Verstreken, Sandra-Fausia Soukup
Neurobiology of Disease. 2022-02-01; 163: 105595
DOI: 10.1016/j.nbd.2021.105595

Read on PubMed

Hernandez-Diaz S(1), Ghimire S(1), Sanchez-Mirasierra I(1), Montecinos-Oliva C(1), Swerts J(2), Kuenen S(2), Verstreken P(2), Soukup SF(3).

Author information:
(1)Univ. Bordeaux, CNRS, IMN, UMR 5293, F-33000 Bordeaux, France.
(2)VIB Center for the Biology of Disease, Belgium; KU Leuven, Department for Human Genetics, Leuven Institute for Neurodegenerative Disease (LIND), 3000 Leuven, Belgium.
(3)Univ. Bordeaux, CNRS, IMN, UMR 5293, F-33000 Bordeaux, France. Electronic address: .

Synapses are critical for neuronal communication and brain function. To maintain neuronal homeostasis, synapses rely on autophagy. Autophagic alterations cause neurodegeneration and synaptic dysfunction is a feature in neurodegenerative diseases. In Parkinson’s disease (PD), where the loss of synapses precedes dopaminergic neuron loss, various PD-causative proteins are involved in the regulation of autophagy. So far only a few factors regulating autophagy at the synapse have been identified and the molecular mechanisms underlying autophagy at the synapse is only partially understood. Here, we describe Endophilin-B (EndoB) as a novel player in the regulation of synaptic autophagy in health and disease. We demonstrate that EndoB is required for autophagosome biogenesis at the synapse, whereas the loss of EndoB blocks the autophagy induction promoted by the PD mutation LRRK2G2019S. We show that EndoB is required to prevent neuronal loss. Moreover, loss of EndoB in the Drosophila visual system leads to an increase in synaptic contacts between photoreceptor terminals and their post-synaptic synapses. These data confirm the role of autophagy in synaptic contact formation and neuronal survival.

Copyright © 2021. Published by Elsevier Inc.


Know more about