Essential role of phosphoinositide metabolism in synaptic vesicle recycling

Ottavio Cremona, Gilbert Di Paolo, Markus R. Wenk, Anita Lüthi, Warren T. Kim, Kohji Takei, Laurie Daniell, Yasuo Nemoto, Stephen B. Shears, Richard A. Flavell, David A. McCormick, Pietro De Camilli

Research output: Contribution to journalArticle

563 Citations (Scopus)

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 languageEnglish
Pages (from-to)179-188
Number of pages10
JournalCell
Volume99
Issue number2
DOIs
Publication statusPublished - 1999
Externally publishedYes

Fingerprint

Synaptic Vesicles
Phosphatidylinositols
Metabolism
Recycling
Clathrin-Coated Vesicles
Clathrin
Nerve Endings
Phosphoric Monoester Hydrolases
Liposomes
Parturition
Neurons
Membranes
Assays
Animals
Proteins
Association reactions
Recovery
Defects
Phosphoinositide Phosphatases
synaptojanin

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

Cremona, O., Di Paolo, G., Wenk, M. R., Lüthi, A., Kim, W. T., Takei, K., ... De Camilli, P. (1999). Essential role of phosphoinositide metabolism in synaptic vesicle recycling. Cell, 99(2), 179-188. https://doi.org/10.1016/S0092-8674(00)81649-9

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 journalArticle

Cremona, O, Di Paolo, G, Wenk, MR, Lüthi, A, Kim, WT, Takei, K, Daniell, L, Nemoto, Y, Shears, SB, Flavell, RA, McCormick, DA & De Camilli, P 1999, 'Essential role of phosphoinositide metabolism in synaptic vesicle recycling', Cell, vol. 99, no. 2, pp. 179-188. https://doi.org/10.1016/S0092-8674(00)81649-9
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. / Essential role of phosphoinositide metabolism in synaptic vesicle recycling. In: Cell. 1999 ; Vol. 99, No. 2. pp. 179-188.
@article{713a582533e34d6c88958400f2a01c3c,
title = "Essential role of phosphoinositide metabolism in synaptic vesicle recycling",
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.",
author = "Ottavio Cremona and {Di Paolo}, Gilbert and Wenk, {Markus R.} and Anita L{\"u}thi and Kim, {Warren T.} and Kohji Takei and Laurie Daniell and Yasuo Nemoto and Shears, {Stephen B.} and Flavell, {Richard A.} and McCormick, {David A.} and {De Camilli}, Pietro",
year = "1999",
doi = "10.1016/S0092-8674(00)81649-9",
language = "English",
volume = "99",
pages = "179--188",
journal = "Cell",
issn = "0092-8674",
publisher = "Cell Press",
number = "2",

}

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.

UR - http://www.scopus.com/inward/record.url?scp=0032736675&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032736675&partnerID=8YFLogxK

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 -