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. 1999 Oct 15;99(2):179-88.
doi: 10.1016/s0092-8674(00)81649-9.

Essential role of phosphoinositide metabolism in synaptic vesicle recycling

O Cremona  1 , G Di Paolo, M R Wenk, A Lüthi, W T Kim, K Takei, L Daniell, Y Nemoto, S B Shears, R A Flavell, D A McCormick, P De Camilli
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Free article

Essential role of phosphoinositide metabolism in synaptic vesicle recycling

O Cremona et al. Cell. .
Free article

Abstract

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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