Essential role of phosphoinositide metabolism in synaptic vesicle recycling.
Cell
; 99(2): 179-88, 1999 Oct 15.
Article
em En
| MEDLINE
| ID: mdl-10535736
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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Base de dados:
MEDLINE
Assunto principal:
Fosfatidilinositóis
/
Vesículas Sinápticas
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Monoéster Fosfórico Hidrolases
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Hipocampo
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Proteínas do Tecido Nervoso
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Neurônios
Idioma:
En
Ano de publicação:
1999
Tipo de documento:
Article