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

Authors
Mani, M; Lee, SY; Lucast, L; Cremona, O; Di Paolo, G; De Camilli, P; Ryan, TA
Citation
Neuron, 56(6):1004-1018, 2007
Journal Title
Neuron
ISSN
0896-62731097-4199
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.
MeSH terms
AnimalsAnimals, NewbornCells, CulturedCerebral Cortex/cytologyElectric Stimulation/methodsEndocytosis/physiology*Endocytosis/radiation effectsMiceMice, KnockoutMicroscopy, ConfocalMolecular Sequence DataMutationNerve Tissue Proteins/deficiencyNerve Tissue Proteins/metabolism*Neurons/cytology*Neurons/radiation effectsPhosphoric Monoester Hydrolases/deficiencyPhosphoric Monoester Hydrolases/metabolismPhosphoric Monoester Hydrolases/physiology*Presynaptic Terminals/physiology*Proline/metabolismProtein BindingProtein Structure, TertiarySynaptic Vesicles/physiology*Synaptic Vesicles/radiation effectsTime FactorsTransfectionsrc Homology Domains/physiology
DOI
10.1016/j.neuron.2007.10.032
PMID
18093523
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Journal Papers > Research Organization > Chronic Inflammatory Disease Research Center
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이, 상윤
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