Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 1 de 1
Filter
Add more filters










Database
Language
Publication year range
1.
Nat Commun ; 7: 12188, 2016 07 19.
Article in English | 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.


Subject(s)
Drosophila Proteins/metabolism , Drosophila melanogaster/metabolism , Leucine-Rich Repeat Serine-Threonine Protein Kinase-2/metabolism , Neuromuscular Junction/metabolism , Synapses/metabolism , Animals , Furin/metabolism , HEK293 Cells , Homeostasis , Humans , Larva/metabolism , Mutant Proteins/metabolism , Mutation/genetics , Neurotransmitter Agents/metabolism , Protein Biosynthesis , RNA Caps/metabolism , Signal Transduction , Synaptic Transmission , Synaptic Vesicles/metabolism
SELECTION OF CITATIONS
SEARCH DETAIL
...