Essential role of phosphoinositide metabolism in synaptic vesicle recycling

Ottavio Cremona, Gilbert Di Paolo, Markus R. Wenk, Anita Lüthi, Warren T. Kim, Kohji Takei, Laurie Daniell, Yasuo Nemoto, Stephen B. Shears, Richard A. Flavell, David A. McCormick, Pietro De Camilli

Research output: Contribution to journalArticlepeer-review

664 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)179-188
Number of pages10
Issue number2
Publication statusPublished - 1999
Externally publishedYes

ASJC Scopus subject areas

  • General Biochemistry,Genetics and Molecular Biology


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