@article{713a582533e34d6c88958400f2a01c3c,
title = "Essential role of phosphoinositide metabolism in synaptic vesicle recycling",
abstract = "Growing evidence suggests that phosphoinositides play an important role in membrane traffic. A poly-phosphoinositide 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.",
author = "Ottavio Cremona and {Di Paolo}, Gilbert and Wenk, {Markus R.} and Anita L{\"u}thi and Kim, {Warren T.} and Kohji Takei and Laurie Daniell and Yasuo Nemoto and Shears, {Stephen B.} and Flavell, {Richard A.} and McCormick, {David A.} and {De Camilli}, Pietro",
note = "Funding Information: We thank Anna Zhang for technical help; Khashayar Farsad for help in electron microscopy experiments; David Brownstein for pathological analysis of mutant mice; Wufan Tao, Di Yang, and Tian Xu for advice in gene targeting; Reinhard Jahn (Gottingen, Germany) for the kind gift of antibodies; and Ezio Perucco and Giuseppe Migliaretti for help in the statistical analysis. This work was supported in part by National Institutes of Health grants to P. D. C. (NS36251 and CA46128) and to D. A. M. (NS26143), by Telethon (project D.61) and MURST (ex-40%) grants to O. C., a Human Frontier Science Program long-term fellowship to O. C. (1996–1997), an EMBO long-term fellowship to G. D. P., a Swiss National Science Foundation grant and a Novartis Stiftung grant to M. W., and a fellowship from the American Epilepsy Foundation to A. L.",
year = "1999",
doi = "10.1016/S0092-8674(00)81649-9",
language = "English",
volume = "99",
pages = "179--188",
journal = "Cell",
issn = "0092-8674",
publisher = "Cell Press",
number = "2",
}