Delayed reentry of recycling vesicles into the fusion-competent synaptic vesicle pool in synaptojanin 1 knockout mice
Open accessAbstract
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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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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- 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
- Publisher
- National Academy of Sciences
- Published
- 2002-12-12
- Volume
- 99
- Issue
- 26
- Pages
- 17143-17148
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC139283
- OpenAlex
- W2048597699
- Cited by
- 123
- References
- 0
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 1 · 2023: 4 · 2022: 4 · 2021: 6 · 2020: 6 · 2019: 8 · 2018: 4 · 2017: 4 · 2016: 5 · 2014: 3 · 2013: 5 · 2012: 9
- FWCI
- 2.55
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- 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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