DOI: 10.1523/jneurosci.2815-04.2004. A New Platform to Study the Molecular Mechanisms of Exocytosis

A New Platform to Study the Molecular Mechanisms of Exocytosis

10.1523/jneurosci.2815-04.2004

Crossref journal-article

Society for Neuroscience

The Journal of Neuroscience (393)

Abstract

The exocytotic process in neurons and neuroendocrine cells consists of a sequence of reactions between well defined proteins. In the present study, we have created for the first time a comprehensive kinetic model that demonstrates the dynamics of interactions between key synaptic proteins that are associated with exocytosis. The interactions between the synaptic proteins were transformed into differential rate equations that, after their integration over time, reconstructed the experimental signal. The model can perfectly reconstruct the kinetics of exocytosis, the calcium-dependent priming and fusion processes, and the effects of genetic manipulation of synaptic proteins. The model suggests that fusion occurs from two parallel pathways and assigns precise, non-identical synaptic protein complexes to the two pathways. In addition, it provides a unique opportunity to study the dynamics of intermediate protein complexes during the fusion process, a possibility that is hidden in most experimental systems. We thus developed a novel approach that allows detailed characterization of the temporal relationship between synaptic protein complexes. This model provides an excellent platform for prediction and quantification of the effects of protein manipulations on exocytosis and opens new avenues for experimental investigation of exocytosis.

Bibliography

Mezer, A., Nachliel, E., Gutman, M., & Ashery, U. (2004). A New Platform to Study the Molecular Mechanisms of Exocytosis. The Journal of Neuroscience, 24(40), 8838â8846.

Authors 4

Aviv Mezer (first)
Esther Nachliel (additional)
Menachem Gutman (additional)
Uri Ashery (additional)

References 47 Referenced 15

10.1093/emboj/19.14.3586
10.1016/S0006-3495(77)85544-6
10.1074/jbc.270.42.25273
10.1038/nrm855
10.1016/S0896-6273(02)00583-4
10.1016/S0896-6273(00)80850-8
10.1523/JNEUROSCI.20-22-08377.2000 / J Neurosci (2000)
10.1113/jphysiol.1967.sp008367 / J Physiol (Lond) (1967)
10.1074/jbc.M312064200
10.1146/annurev.physiol.61.1.753
10.1074/jbc.275.9.6328
10.1074/jbc.M400827200
10.1016/0301-4622(79)85012-7 / Biophys Chem (1979)
10.1016/S0006-3495(94)80744-1
10.1146/annurev.biochem.68.1.863
10.1093/emboj/20.9.2202
Lindfield G, Penny J (1995) Numerical methods using MATLAB. New York: Ellis Horwood.
10.1007/BF02331827
10.1073/pnas.2331232100
10.1016/S0166-2236(02)02207-5
10.1529/biophysj.104.039925
10.1073/pnas.94.13.6735
10.1016/S0896-6273(00)80983-6
10.1074/jbc.M109507200
10.1016/S0092-8674(01)00192-1
10.1126/science.1075375
10.1016/S0092-8674(01)00635-3
10.1016/S0959-4388(02)00360-4
10.1074/jbc.C200692200
10.1074/jbc.M310879200
10.1016/j.conb.2003.09.011
10.1016/S0896-6273(00)80504-8
10.1073/pnas.251673298
10.1085/jgp.200308855
10.1016/S0896-6273(00)00109-4
10.1074/jbc.R100052200
10.1038/26412
10.1016/S0896-6273(00)00131-8
10.1016/S0896-6273(00)80812-0
10.1073/pnas.201398798
10.1126/science.8235626
10.1083/jcb.128.4.637
10.1016/S0092-8674(00)81404-X
10.1073/pnas.2036428100
10.1038/642
10.1074/jbc.273.47.31297
10.1016/S0896-6273(02)00671-2

Dates

Type	When
Created	20 years, 10 months ago (Oct. 6, 2004, 2:22 p.m.)
Deposited	2 years, 4 months ago (April 13, 2023, 12:24 p.m.)
Indexed	3 months, 1 week ago (May 28, 2025, 2:02 p.m.)
Issued	20 years, 10 months ago (Oct. 6, 2004)
Published	20 years, 10 months ago (Oct. 6, 2004)
Published Online	20 years, 10 months ago (Oct. 6, 2004)
Published Print	20 years, 10 months ago (Oct. 6, 2004)

Funders 0

None

BibTeX

@article{Mezer_2004, title={A New Platform to Study the Molecular Mechanisms of Exocytosis}, volume={24}, ISSN={1529-2401}, url={http://dx.doi.org/10.1523/jneurosci.2815-04.2004}, DOI={10.1523/jneurosci.2815-04.2004}, number={40}, journal={The Journal of Neuroscience}, publisher={Society for Neuroscience}, author={Mezer, Aviv and Nachliel, Esther and Gutman, Menachem and Ashery, Uri}, year={2004}, month=oct, pages={8838–8846} }

JSON

{
  "indexed": {
    "date-parts": [
      [
        2025,
        5,
        28
      ]
    ],
    "date-time": "2025-05-28T18:02:21Z",
    "timestamp": 1748455341449
  },
  "reference-count": 47,
  "publisher": "Society for Neuroscience",
  "issue": "40",
  "license": [
    {
      "start": {
        "date-parts": [
          [
            2005,
            4,
            6
          ]
        ],
        "date-time": "2005-04-06T00:00:00Z",
        "timestamp": 1112745600000
      },
      "content-version": "vor",
      "delay-in-days": 182,
      "URL": "https://creativecommons.org/licenses/by-nc-sa/4.0/"
    }
  ],
  "content-domain": {
    "domain": [],
    "crossmark-restriction": false
  },
  "published-print": {
    "date-parts": [
      [
        2004,
        10,
        6
      ]
    ]
  },
  "abstract": "<jats:p>The exocytotic process in neurons and neuroendocrine cells consists of a sequence of reactions between well defined proteins. In the present study, we have created for the first time a comprehensive kinetic model that demonstrates the dynamics of interactions between key synaptic proteins that are associated with exocytosis. The interactions between the synaptic proteins were transformed into differential rate equations that, after their integration over time, reconstructed the experimental signal. The model can perfectly reconstruct the kinetics of exocytosis, the calcium-dependent priming and fusion processes, and the effects of genetic manipulation of synaptic proteins. The model suggests that fusion occurs from two parallel pathways and assigns precise, non-identical synaptic protein complexes to the two pathways. In addition, it provides a unique opportunity to study the dynamics of intermediate protein complexes during the fusion process, a possibility that is hidden in most experimental systems. We thus developed a novel approach that allows detailed characterization of the temporal relationship between synaptic protein complexes. This model provides an excellent platform for prediction and quantification of the effects of protein manipulations on exocytosis and opens new avenues for experimental investigation of exocytosis.</jats:p>",
  "DOI": "10.1523/jneurosci.2815-04.2004",
  "type": "journal-article",
  "created": {
    "date-parts": [
      [
        2004,
        10,
        6
      ]
    ],
    "date-time": "2004-10-06T18:22:57Z",
    "timestamp": 1097086977000
  },
  "page": "8838-8846",
  "source": "Crossref",
  "is-referenced-by-count": 15,
  "title": "A New Platform to Study the Molecular Mechanisms of Exocytosis",
  "prefix": "10.1523",
  "volume": "24",
  "author": [
    {
      "given": "Aviv",
      "family": "Mezer",
      "sequence": "first",
      "affiliation": []
    },
    {
      "given": "Esther",
      "family": "Nachliel",
      "sequence": "additional",
      "affiliation": []
    },
    {
      "given": "Menachem",
      "family": "Gutman",
      "sequence": "additional",
      "affiliation": []
    },
    {
      "given": "Uri",
      "family": "Ashery",
      "sequence": "additional",
      "affiliation": []
    }
  ],
  "member": "393",
  "published-online": {
    "date-parts": [
      [
        2004,
        10,
        6
      ]
    ]
  },
  "reference": [
    {
      "key": "2023041303085820000_24.40.8838.1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1093/emboj/19.14.3586"
    },
    {
      "key": "2023041303085820000_24.40.8838.2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0006-3495(77)85544-6"
    },
    {
      "key": "2023041303085820000_24.40.8838.3",
      "doi-asserted-by": "publisher",
      "DOI": "10.1074/jbc.270.42.25273"
    },
    {
      "key": "2023041303085820000_24.40.8838.4",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/nrm855"
    },
    {
      "key": "2023041303085820000_24.40.8838.5",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0896-6273(02)00583-4"
    },
    {
      "key": "2023041303085820000_24.40.8838.6",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0896-6273(00)80850-8"
    },
    {
      "key": "2023041303085820000_24.40.8838.7",
      "doi-asserted-by": "crossref",
      "first-page": "8377",
      "DOI": "10.1523/JNEUROSCI.20-22-08377.2000",
      "volume": "20",
      "year": "2000",
      "journal-title": "J Neurosci"
    },
    {
      "key": "2023041303085820000_24.40.8838.8",
      "doi-asserted-by": "crossref",
      "first-page": "419",
      "DOI": "10.1113/jphysiol.1967.sp008367",
      "volume": "193",
      "year": "1967",
      "journal-title": "J Physiol (Lond)"
    },
    {
      "key": "2023041303085820000_24.40.8838.9",
      "doi-asserted-by": "publisher",
      "DOI": "10.1074/jbc.M312064200"
    },
    {
      "key": "2023041303085820000_24.40.8838.10",
      "doi-asserted-by": "publisher",
      "DOI": "10.1146/annurev.physiol.61.1.753"
    },
    {
      "key": "2023041303085820000_24.40.8838.11",
      "doi-asserted-by": "publisher",
      "DOI": "10.1074/jbc.275.9.6328"
    },
    {
      "key": "2023041303085820000_24.40.8838.12",
      "doi-asserted-by": "publisher",
      "DOI": "10.1074/jbc.M400827200"
    },
    {
      "key": "2023041303085820000_24.40.8838.13",
      "doi-asserted-by": "crossref",
      "first-page": "239",
      "DOI": "10.1016/0301-4622(79)85012-7",
      "volume": "10",
      "year": "1979",
      "journal-title": "Biophys Chem"
    },
    {
      "key": "2023041303085820000_24.40.8838.14",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0006-3495(94)80744-1"
    },
    {
      "key": "2023041303085820000_24.40.8838.15",
      "doi-asserted-by": "publisher",
      "DOI": "10.1146/annurev.biochem.68.1.863"
    },
    {
      "key": "2023041303085820000_24.40.8838.16",
      "doi-asserted-by": "publisher",
      "DOI": "10.1093/emboj/20.9.2202"
    },
    {
      "key": "2023041303085820000_24.40.8838.17",
      "unstructured": "Lindfield G, Penny J (1995) Numerical methods using MATLAB. New York: Ellis Horwood."
    },
    {
      "key": "2023041303085820000_24.40.8838.18",
      "doi-asserted-by": "publisher",
      "DOI": "10.1007/BF02331827"
    },
    {
      "key": "2023041303085820000_24.40.8838.19",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.2331232100"
    },
    {
      "key": "2023041303085820000_24.40.8838.20",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0166-2236(02)02207-5"
    },
    {
      "key": "2023041303085820000_24.40.8838.21",
      "doi-asserted-by": "publisher",
      "DOI": "10.1529/biophysj.104.039925"
    },
    {
      "key": "2023041303085820000_24.40.8838.22",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.94.13.6735"
    },
    {
      "key": "2023041303085820000_24.40.8838.23",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0896-6273(00)80983-6"
    },
    {
      "key": "2023041303085820000_24.40.8838.24",
      "doi-asserted-by": "publisher",
      "DOI": "10.1074/jbc.M109507200"
    },
    {
      "key": "2023041303085820000_24.40.8838.25",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0092-8674(01)00192-1"
    },
    {
      "key": "2023041303085820000_24.40.8838.26",
      "doi-asserted-by": "publisher",
      "DOI": "10.1126/science.1075375"
    },
    {
      "key": "2023041303085820000_24.40.8838.27",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0092-8674(01)00635-3"
    },
    {
      "key": "2023041303085820000_24.40.8838.28",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0959-4388(02)00360-4"
    },
    {
      "key": "2023041303085820000_24.40.8838.29",
      "doi-asserted-by": "publisher",
      "DOI": "10.1074/jbc.C200692200"
    },
    {
      "key": "2023041303085820000_24.40.8838.30",
      "doi-asserted-by": "publisher",
      "DOI": "10.1074/jbc.M310879200"
    },
    {
      "key": "2023041303085820000_24.40.8838.31",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/j.conb.2003.09.011"
    },
    {
      "key": "2023041303085820000_24.40.8838.32",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0896-6273(00)80504-8"
    },
    {
      "key": "2023041303085820000_24.40.8838.33",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.251673298"
    },
    {
      "key": "2023041303085820000_24.40.8838.34",
      "doi-asserted-by": "publisher",
      "DOI": "10.1085/jgp.200308855"
    },
    {
      "key": "2023041303085820000_24.40.8838.35",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0896-6273(00)00109-4"
    },
    {
      "key": "2023041303085820000_24.40.8838.36",
      "doi-asserted-by": "publisher",
      "DOI": "10.1074/jbc.R100052200"
    },
    {
      "key": "2023041303085820000_24.40.8838.37",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/26412"
    },
    {
      "key": "2023041303085820000_24.40.8838.38",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0896-6273(00)00131-8"
    },
    {
      "key": "2023041303085820000_24.40.8838.39",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0896-6273(00)80812-0"
    },
    {
      "key": "2023041303085820000_24.40.8838.40",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.201398798"
    },
    {
      "key": "2023041303085820000_24.40.8838.41",
      "doi-asserted-by": "publisher",
      "DOI": "10.1126/science.8235626"
    },
    {
      "key": "2023041303085820000_24.40.8838.42",
      "doi-asserted-by": "publisher",
      "DOI": "10.1083/jcb.128.4.637"
    },
    {
      "key": "2023041303085820000_24.40.8838.43",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0092-8674(00)81404-X"
    },
    {
      "key": "2023041303085820000_24.40.8838.44",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.2036428100"
    },
    {
      "key": "2023041303085820000_24.40.8838.45",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/642"
    },
    {
      "key": "2023041303085820000_24.40.8838.46",
      "doi-asserted-by": "publisher",
      "DOI": "10.1074/jbc.273.47.31297"
    },
    {
      "key": "2023041303085820000_24.40.8838.47",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0896-6273(02)00671-2"
    }
  ],
  "container-title": "The Journal of Neuroscience",
  "original-title": [],
  "language": "en",
  "link": [
    {
      "URL": "https://syndication.highwire.org/content/doi/10.1523/JNEUROSCI.2815-04.2004",
      "content-type": "unspecified",
      "content-version": "vor",
      "intended-application": "similarity-checking"
    }
  ],
  "deposited": {
    "date-parts": [
      [
        2023,
        4,
        13
      ]
    ],
    "date-time": "2023-04-13T16:24:19Z",
    "timestamp": 1681403059000
  },
  "score": 1,
  "resource": {
    "primary": {
      "URL": "https://www.jneurosci.org/lookup/doi/10.1523/JNEUROSCI.2815-04.2004"
    }
  },
  "subtitle": [],
  "short-title": [],
  "issued": {
    "date-parts": [
      [
        2004,
        10,
        6
      ]
    ]
  },
  "references-count": 47,
  "journal-issue": {
    "issue": "40",
    "published-online": {
      "date-parts": [
        [
          2004,
          10,
          6
        ]
      ]
    },
    "published-print": {
      "date-parts": [
        [
          2004,
          10,
          6
        ]
      ]
    }
  },
  "alternative-id": [
    "10.1523/JNEUROSCI.2815-04.2004"
  ],
  "URL": "http://dx.doi.org/10.1523/JNEUROSCI.2815-04.2004",
  "relation": {},
  "ISSN": [
    "0270-6474",
    "1529-2401"
  ],
  "subject": [],
  "container-title-short": "J. Neurosci.",
  "published": {
    "date-parts": [
      [
        2004,
        10,
        6
      ]
    ]
  }
}