Department of Anesthesiology

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The dual phosphatase activity of synaptojanin1 is required for both efficient synaptic vesicle endocytosis and reavailability at nerve terminals.

TitleThe dual phosphatase activity of synaptojanin1 is required for both efficient synaptic vesicle endocytosis and reavailability at nerve terminals.
Publication TypeJournal Article
Year of Publication2007
AuthorsMani M, Lee SYoon, Lucast L, Cremona O, Di Paolo G, De Camilli P, Ryan TA
JournalNeuron
Volume56
Issue6
Pagination1004-18
Date Published2007 Dec 20
ISSN0896-6273
KeywordsAnimals, Animals, Newborn, Cells, Cultured, Cerebral Cortex, Electric Stimulation, Endocytosis, Mice, Mice, Knockout, Microscopy, Confocal, Molecular Sequence Data, Mutation, Nerve Tissue Proteins, Neurons, Phosphoric Monoester Hydrolases, Presynaptic Terminals, Proline, Protein Binding, Protein Structure, Tertiary, src Homology Domains, Synaptic Vesicles, Time Factors, Transfection
Abstract

Phosphoinositides have been implicated in synaptic vesicle recycling largely based on studies of enzymes that regulate phosphoinositide synthesis and hydrolysis. One such enzyme is synaptojanin1, a multifunctional protein conserved from yeast to humans, which contains two phosphoinositol phosphatase domains and a proline-rich domain. Genetic ablation of synaptojanin1 leads to pleiotropic defects in presynaptic function, including accumulation of free clathrin-coated vesicles and delayed vesicle reavailability, implicating this enzyme in postendocytic uncoating of vesicles. To further elucidate the role of synaptojanin1 at nerve terminals, we performed quantitative synaptic vesicle recycling assays in synj1(-/-) neurons. Our studies show that synaptojanin1 is also required for normal vesicle endocytosis. Defects in both endocytosis and postendocytic vesicle reavailability can be fully restored upon reintroduction of synaptojanin1. However, expression of synaptojanin1 with mutations abolishing catalytic activity of each phosphatase domain reveals that the dual action of both domains is required for normal synaptic vesicle internalization and reavailability.

DOI10.1016/j.neuron.2007.10.032
Alternate JournalNeuron
PubMed ID18093523
PubMed Central IDPMC3653591
Grant ListCA46128 / CA / NCI NIH HHS / United States
GM07739 / GM / NIGMS NIH HHS / United States
NS036251 / NS / NINDS NIH HHS / United States
NS036942 / NS / NINDS NIH HHS / United States
NS056049 / NS / NINDS NIH HHS / United States
P30 DA018343 / DA / NIDA NIH HHS / United States
R01 NS036942 / NS / NINDS NIH HHS / United States