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Essential Role of Phosphoinositide Metabolism in Synaptic Vesicle Recycling
Open accessAbstract
Growing evidence suggests that phosphoinositides play an important role in membrane traffic. A polyphosphoinositide phosphatase, synaptojanin 1, was identified as a major presynaptic protein associated with endocytic coated intermediates. We report here that synaptojanin 1-deficient mice exhibit neurological defects and die shortly after birth. In neurons of mutant animals, PI(4,5)P2 levels are increased, and clathrin-coated vesicles accumulate in the cytomatrix-rich area that surrounds the synaptic vesicle cluster in nerve endings. In cell-free assays, reduced phosphoinositide phosphatase activity correlated with increased association of clathrin coats with liposomes. Intracellular recording in hippocampal slices revealed enhanced synaptic depression during prolonged high-frequency stimulation followed by delayed recovery. These results provide genetic evidence for a crucial role of phosphoinositide metabolism in synaptic vesicle recycling.
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Metadata
- Authors
- Cremona, O., Di Paolo, G., Wenk, M. R., Lüthi, A., Kim, W. T., Takei, K., Daniell, L., Nemoto, Y., Shears, S. B., Flavell, R. A., McCormick, D. A., & De Camilli, P.
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 1999-10
- Volume
- 99
- Issue
- 2
- Pages
- 179-188
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W1965940344
- Cited by
- 834
- References
- 2
- FWCI
- 14.13
- Type
- journal article
- Language
- en
- Open access
- hybrid
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