Cited by 123Cellular transport and secretionNeuroscience and Neuropharmacology ResearchExtracellular vesicles in disease

Delayed reentry of recycling vesicles into the fusion-competent synaptic vesicle pool in synaptojanin 1 knockout mice

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Kim, Warren T., Chang, Sunghoe, Daniell, Laurie, Cremona, Ottavio, Di Paolo, Gilbert, De Camilli, Pietro·2002·Proceedings of the National Academy of Sciences

Abstract

Synaptojanin 1 is a polyphosphoinositide phosphatase implicated in synaptic vesicle recycling. We used FM1-43 imaging and electron microscopy in cultured cortical neurons from control and synaptojanin 1 knockout mice to study how the absence of this protein affects specific steps of the synaptic vesicle cycle. Exo/endocytosis after a moderate stimulus was unchanged. However, during prolonged stimulation, the regeneration of fusion-competent synaptic vesicles was severely impaired. In stimulated nerve terminals, there was a persistent accumulation of clathrin-coated vesicles and a backup of newly reformed vesicles in the cytomatrix-rich area around the synaptic vesicle cluster. These findings demonstrate that synaptojanin 1 function is needed for the progression of recycling vesicles to the functional synaptic vesicle pool.

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Crossref · 10.1073/pnas.222657399

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  • PI(4,5)P2 is dephosphorylated by 5-phosphatases for uncoating to take place; excess PI(4,5)P2 inhibits endocytosis by preventing uncoating and subsequent vesicular fusion.

    “PI(4,5)P2 is dephosphorylated by 5-phosphatases for uncoating to take place [104]. Thus, although PI(4,5)P2 facilitates the mechanism of clathrin vesicle endocytosis, excess PI(4,5)P2 inhibits endocytosis. Persistence of PI(4,5)P2 on vesicular membranes prevents the uncoating of the vesicle and subsequent vesicular fusion with the target membrane [105].”

    From Phosphatidylinositol(4,5)bisphosphate: diverse functions at the plasma membrane (2020) · cites this paper as [105]

    The Discussion (page unavailable) proposes that persistently high PI(4,5)P2 may delay vesicle uncoating and reports impaired reentry into the functional synaptic-vesicle pool. It does not show that uncoating is prevented or that fusion with a target membrane is blocked; the Results say coated vesicles eventually uncoat. The dephosphorylation statement is attached to citation [104], not this source’s citation [105]. (LLM, conf=0.88)

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Cited by

Sorted by citations

Authors
Kim, W. T., Chang, S., Daniell, L., Cremona, O., Di Paolo, G., & De Camilli, P.
Affiliations
  • Howard Hughes Medical Institute (US)
  • Howard Hughes Medical Institute and Department of Cell Biology, Yale University School of Medicine, 295 Congress Avenue, New Haven, CT 06510; and Università Vita–Salute San Raffaele, Via Olgettina 58, Milan 20132, Italy
Venue
Proceedings of the National Academy of Sciences
Published
2002-12-12
Volume
99
Issue
26
Pages
17143-17148
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
OpenAlex
W2048597699
Cited by
123
References
0
Citations by year
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FWCI
2.55
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Cancer Institute (P01CA046128, CA46128)
  • National Institute of Neurological Disorders and Stroke (R01NS036251, R37NS036251, NS 63251)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
Keywords
SYNJ1, synaptic vesicle recycling, clathrin-coated vesicles, knockout mice, cortical neurons
MeSH terms
Animals, Cell Fusion, Cells, Cultured, Cerebral Cortex, Endocytosis, Exocytosis, Microscopy, Electron, Nerve Tissue Proteins, Phosphoric Monoester Hydrolases, Synaptic Vesicles, Mice, Knockout, Clathrin-Coated Vesicles, Mice

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