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Publication : Essential role of phosphoinositide metabolism in synaptic vesicle recycling.

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.
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