Abstract
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 language | English |
|---|---|
| Pages (from-to) | 179-188 |
| Number of pages | 10 |
| Journal | Cell |
| Volume | 99 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - 1999 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Cell Biology
- Molecular Biology
Cite this
Essential role of phosphoinositide metabolism in synaptic vesicle recycling. / Cremona, Ottavio; Di Paolo, Gilbert; Wenk, Markus R.; Lüthi, Anita; Kim, Warren T.; Takei, Kohji; Daniell, Laurie; Nemoto, Yasuo; Shears, Stephen B.; Flavell, Richard A.; McCormick, David A.; De Camilli, Pietro.
In: Cell, Vol. 99, No. 2, 1999, p. 179-188.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Essential role of phosphoinositide metabolism in synaptic vesicle recycling
AU - Cremona, Ottavio
AU - Di Paolo, Gilbert
AU - Wenk, Markus R.
AU - Lüthi, Anita
AU - Kim, Warren T.
AU - Takei, Kohji
AU - Daniell, Laurie
AU - Nemoto, Yasuo
AU - Shears, Stephen B.
AU - Flavell, Richard A.
AU - McCormick, David A.
AU - De Camilli, Pietro
PY - 1999
Y1 - 1999
N2 - 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.
AB - 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.
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U2 - 10.1016/S0092-8674(00)81649-9
DO - 10.1016/S0092-8674(00)81649-9
M3 - Article
VL - 99
SP - 179
EP - 188
JO - Cell
JF - Cell
SN - 0092-8674
IS - 2
ER -