First Author | Cremona O | Year | 1999 |
Journal | Cell | Volume | 99 |
Issue | 2 | Pages | 179-88 |
PubMed ID | 10535736 | Mgi Jnum | J:58087 |
Mgi Id | MGI:1346710 | Doi | 10.1016/s0092-8674(00)81649-9 |
Citation | Cremona O, et al. (1999) Essential role of phosphoinositide metabolism in synaptic vesicle recycling. Cell 99(2):179-88 |
abstractText | 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. |