Preparing your results

Our searching services are busy right now. Your search will reload in five seconds.

X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

LRRK2 controls an EndoA phosphorylation cycle in synaptic endocytosis.

Neuron | Sep 20, 2012

http://www.ncbi.nlm.nih.gov/pubmed/22998870

LRRK2 is a kinase mutated in Parkinson's disease, but how the protein affects synaptic function remains enigmatic. We identified LRRK2 as a critical regulator of EndophilinA. Using genetic and biochemical studies involving Lrrk loss-of-function mutants and Parkinson-related LRRK2(G2019S) gain-of-kinase function, we show that LRRK2 affects synaptic endocytosis by phosphorylating EndoA at S75, a residue in the BAR domain. We show that LRRK2-mediated EndoA phosphorylation has profound effects on EndoA-dependent membrane tubulation and membrane association in vitro and in vivo and on synaptic vesicle endocytosis at Drosophila neuromuscular junctions in vivo. Our work uncovers a regulatory mechanism that indicates that reduced LRRK2 kinase activity facilitates EndoA membrane association, while increased kinase activity inhibits membrane association. Consequently, both too much and too little LRRK2-dependent EndoA phosphorylation impedes synaptic endocytosis, and we propose a model in which LRRK2 kinase activity is part of an EndoA phosphorylation cycle that facilitates efficient vesicle formation at synapses.

Pubmed ID: 22998870 RIS Download

Mesh terms: Acyltransferases | Animals | Animals, Genetically Modified | Brain | CHO Cells | Calcium | Clathrin | Cricetinae | Drosophila | Drosophila Proteins | Endocytosis | Gene Expression Regulation | Green Fluorescent Proteins | Humans | Mass Spectrometry | Mice | Microscopy, Electron, Transmission | Models, Molecular | Mutation | Neuromuscular Junction | Phosphorylation | Protein-Serine-Threonine Kinases | RNA, Small Interfering | Sequence Alignment | Serine | Synaptic Potentials | Synaptic Vesicles | Transfection

Research resources used in this publication

Research tools detected in this publication

None found

Data used in this publication

None found

Associated grants

None

Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.