LRRK2 regulates retrograde synaptic compensation at the Drosophila neuromuscular junction.
Nat Commun
; 7: 12188, 2016 07 19.
Article
em En
| MEDLINE
| ID: mdl-27432119
ABSTRACT
Parkinson's disease gene leucine-rich repeat kinase 2 (LRRK2) has been implicated in a number of processes including the regulation of mitochondrial function, autophagy and endocytic dynamics; nevertheless, we know little about its potential role in the regulation of synaptic plasticity. Here we demonstrate that postsynaptic knockdown of the fly homologue of LRRK2 thwarts retrograde, homeostatic synaptic compensation at the larval neuromuscular junction. Conversely, postsynaptic overexpression of either the fly or human LRRK2 transgene induces a retrograde enhancement of presynaptic neurotransmitter release by increasing the size of the release ready pool of vesicles. We show that LRRK2 promotes cap-dependent translation and identify Furin 1 as its translational target, which is required for the synaptic function of LRRK2. As the regulation of synaptic homeostasis plays a fundamental role in ensuring normal and stable synaptic function, our findings suggest that aberrant function of LRRK2 may lead to destabilization of neural circuits.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Sinapses
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Proteínas de Drosophila
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Drosophila melanogaster
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Serina-Treonina Proteína Quinase-2 com Repetições Ricas em Leucina
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Junção Neuromuscular
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article