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PMID:18093523

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Citation

Mani, M, Lee, SY, Lucast, L, Cremona, O, Di Paolo, G, De Camilli, P and Ryan, TA (2007) The dual phosphatase activity of synaptojanin1 is required for both efficient synaptic vesicle endocytosis and reavailability at nerve terminals. Neuron 56:1004-18

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.

Links

PubMed Online version:10.1016/j.neuron.2007.10.032

Keywords

Animals; Animals, Newborn; Cells, Cultured; Cerebral Cortex/cytology; Electric Stimulation/methods; Endocytosis/physiology; Endocytosis/radiation effects; Mice; Mice, Knockout; Microscopy, Confocal; Molecular Sequence Data; Mutation; Nerve Tissue Proteins/deficiency; Nerve Tissue Proteins/metabolism; Neurons/cytology; Neurons/radiation effects; Phosphoric Monoester Hydrolases/deficiency; Phosphoric Monoester Hydrolases/metabolism; Phosphoric Monoester Hydrolases/physiology; Presynaptic Terminals/physiology; Proline/metabolism; Protein Binding; Protein Structure, Tertiary; Synaptic Vesicles/physiology; Synaptic Vesicles/radiation effects; Time Factors; Transfection; src Homology Domains/physiology

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:SYNJ1

located_in

GO:0098793: presynapse

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:SYNJ1

enables

GO:0004438: phosphatidylinositol-3-phosphatase activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

HUMAN:SYNJ1

enables

GO:0004439: phosphatidylinositol-4,5-bisphosphate 5-phosphatase activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

HUMAN:SYNJ1

enables

GO:0043812: phosphatidylinositol-4-phosphate phosphatase activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

HUMAN:SYNJ1

involved_in

GO:0048488: synaptic vesicle endocytosis

ECO:0000316: genetic interaction evidence used in manual assertion

UniProtKB:Q8CHC4

P

Seeded From UniProt

complete

HUMAN:SYNJ1

involved_in

GO:0046856: phosphatidylinositol dephosphorylation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:SH3G2

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

PR:Q8CHC4

F

Seeded From UniProt

complete

MOUSE:AMPH

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

PR:Q8CHC4

F

Seeded From UniProt

complete

MOUSE:SYNJ1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

PR:Q62420
PR:Q7TQF7

F

Seeded From UniProt

complete

MOUSE:SYNJ1

enables

GO:0034595: phosphatidylinositol phosphate 5-phosphatase activity

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2179801

F

Seeded From UniProt

complete

MOUSE:SYNJ1

acts_upstream_of_or_within

GO:0048488: synaptic vesicle endocytosis

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2179801

P

Seeded From UniProt

complete


See also

References

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