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<title xml:lang="en">Sustained synaptic-vesicle recycling by bulk endocytosis contributes to the maintenance of high-rate neurotransmitter release stimulated by glycerotoxin</title>
<author>
<name sortKey="Meunier, Frederic A" sort="Meunier, Frederic A" uniqKey="Meunier F" first="Frederic A." last="Meunier">Frederic A. Meunier</name>
<affiliation>
<nlm:aff id="A1">
<institution>Molecular Dynamics of Synaptic Function Laboratory, Queensland Brain Institute and School of Biomedical Sciences, The University of Queensland</institution>
,
<addr-line>Brisbane QLD 4072</addr-line>
,
<country>Australia</country>
</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Nguyen, Tam H" sort="Nguyen, Tam H" uniqKey="Nguyen T" first="Tam H." last="Nguyen">Tam H. Nguyen</name>
<affiliation>
<nlm:aff id="A1">
<institution>Molecular Dynamics of Synaptic Function Laboratory, Queensland Brain Institute and School of Biomedical Sciences, The University of Queensland</institution>
,
<addr-line>Brisbane QLD 4072</addr-line>
,
<country>Australia</country>
</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Colasante, Cesare" sort="Colasante, Cesare" uniqKey="Colasante C" first="Cesare" last="Colasante">Cesare Colasante</name>
<affiliation>
<nlm:aff id="A2">
<institution>Laboratorio de Fisiología de la Conducta, Facultad de Medicina, Universidad de Los Andes</institution>
,
<addr-line>Mérida 5101</addr-line>
,
<country>Venezuela</country>
</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Luo, Fujun" sort="Luo, Fujun" uniqKey="Luo F" first="Fujun" last="Luo">Fujun Luo</name>
<affiliation>
<nlm:aff id="A3">
<institution>Department of Neuroscience, University of Pittsburgh</institution>
,
<addr-line>Pittsburgh, PA 15260</addr-line>
,
<country>USA</country>
</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Sullivan, Robert K P" sort="Sullivan, Robert K P" uniqKey="Sullivan R" first="Robert K. P." last="Sullivan">Robert K. P. Sullivan</name>
<affiliation>
<nlm:aff id="A1">
<institution>Molecular Dynamics of Synaptic Function Laboratory, Queensland Brain Institute and School of Biomedical Sciences, The University of Queensland</institution>
,
<addr-line>Brisbane QLD 4072</addr-line>
,
<country>Australia</country>
</nlm:aff>
</affiliation>
<affiliation>
<nlm:aff id="A4">
<institution>Centre for Microscopy and Microanalysis, The University of Queensland</institution>
,
<addr-line>Brisbane QLD 4072</addr-line>
,
<country>Australia</country>
</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Lavidis, Nickolas A" sort="Lavidis, Nickolas A" uniqKey="Lavidis N" first="Nickolas A." last="Lavidis">Nickolas A. Lavidis</name>
<affiliation>
<nlm:aff id="A5">
<institution>School of Biomedical Sciences, The University of Queensland</institution>
,
<addr-line>Brisbane QLD 4072</addr-line>
,
<country>Australia</country>
</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Molg, Jordi" sort="Molg, Jordi" uniqKey="Molg J" first="Jordi" last="Molg">Jordi Molg</name>
<affiliation>
<nlm:aff id="A6">
<institution>CNRS, Institut de Neurobiologie Alfred Fessard – FRC2118, Laboratoire de Neurobiologie Cellulaire et Moléculaire – UPR9040</institution>
,
<addr-line>1 Avenue de la Terrasse, 91198 Gif sur Yvette</addr-line>
,
<country>France</country>
</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Meriney, Stephen D" sort="Meriney, Stephen D" uniqKey="Meriney S" first="Stephen D." last="Meriney">Stephen D. Meriney</name>
<affiliation>
<nlm:aff id="A3">
<institution>Department of Neuroscience, University of Pittsburgh</institution>
,
<addr-line>Pittsburgh, PA 15260</addr-line>
,
<country>USA</country>
</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Schiavo, Giampietro" sort="Schiavo, Giampietro" uniqKey="Schiavo G" first="Giampietro" last="Schiavo">Giampietro Schiavo</name>
<affiliation>
<nlm:aff id="A7">
<institution>Molecular Neuropathobiology Laboratory, Cancer Research UK London Research Institute, Lincoln's Inn Fields Laboratories</institution>
,
<addr-line>London WC2A 3PX</addr-line>
,
<country>UK</country>
</nlm:aff>
</affiliation>
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<idno type="pmid">20215402</idno>
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<idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2844322</idno>
<idno type="RBID">PMC:2844322</idno>
<idno type="doi">10.1242/jcs.049296</idno>
<date when="2010">2010</date>
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<title xml:lang="en" level="a" type="main">Sustained synaptic-vesicle recycling by bulk endocytosis contributes to the maintenance of high-rate neurotransmitter release stimulated by glycerotoxin</title>
<author>
<name sortKey="Meunier, Frederic A" sort="Meunier, Frederic A" uniqKey="Meunier F" first="Frederic A." last="Meunier">Frederic A. Meunier</name>
<affiliation>
<nlm:aff id="A1">
<institution>Molecular Dynamics of Synaptic Function Laboratory, Queensland Brain Institute and School of Biomedical Sciences, The University of Queensland</institution>
,
<addr-line>Brisbane QLD 4072</addr-line>
,
<country>Australia</country>
</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Nguyen, Tam H" sort="Nguyen, Tam H" uniqKey="Nguyen T" first="Tam H." last="Nguyen">Tam H. Nguyen</name>
<affiliation>
<nlm:aff id="A1">
<institution>Molecular Dynamics of Synaptic Function Laboratory, Queensland Brain Institute and School of Biomedical Sciences, The University of Queensland</institution>
,
<addr-line>Brisbane QLD 4072</addr-line>
,
<country>Australia</country>
</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Colasante, Cesare" sort="Colasante, Cesare" uniqKey="Colasante C" first="Cesare" last="Colasante">Cesare Colasante</name>
<affiliation>
<nlm:aff id="A2">
<institution>Laboratorio de Fisiología de la Conducta, Facultad de Medicina, Universidad de Los Andes</institution>
,
<addr-line>Mérida 5101</addr-line>
,
<country>Venezuela</country>
</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Luo, Fujun" sort="Luo, Fujun" uniqKey="Luo F" first="Fujun" last="Luo">Fujun Luo</name>
<affiliation>
<nlm:aff id="A3">
<institution>Department of Neuroscience, University of Pittsburgh</institution>
,
<addr-line>Pittsburgh, PA 15260</addr-line>
,
<country>USA</country>
</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Sullivan, Robert K P" sort="Sullivan, Robert K P" uniqKey="Sullivan R" first="Robert K. P." last="Sullivan">Robert K. P. Sullivan</name>
<affiliation>
<nlm:aff id="A1">
<institution>Molecular Dynamics of Synaptic Function Laboratory, Queensland Brain Institute and School of Biomedical Sciences, The University of Queensland</institution>
,
<addr-line>Brisbane QLD 4072</addr-line>
,
<country>Australia</country>
</nlm:aff>
</affiliation>
<affiliation>
<nlm:aff id="A4">
<institution>Centre for Microscopy and Microanalysis, The University of Queensland</institution>
,
<addr-line>Brisbane QLD 4072</addr-line>
,
<country>Australia</country>
</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Lavidis, Nickolas A" sort="Lavidis, Nickolas A" uniqKey="Lavidis N" first="Nickolas A." last="Lavidis">Nickolas A. Lavidis</name>
<affiliation>
<nlm:aff id="A5">
<institution>School of Biomedical Sciences, The University of Queensland</institution>
,
<addr-line>Brisbane QLD 4072</addr-line>
,
<country>Australia</country>
</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Molg, Jordi" sort="Molg, Jordi" uniqKey="Molg J" first="Jordi" last="Molg">Jordi Molg</name>
<affiliation>
<nlm:aff id="A6">
<institution>CNRS, Institut de Neurobiologie Alfred Fessard – FRC2118, Laboratoire de Neurobiologie Cellulaire et Moléculaire – UPR9040</institution>
,
<addr-line>1 Avenue de la Terrasse, 91198 Gif sur Yvette</addr-line>
,
<country>France</country>
</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Meriney, Stephen D" sort="Meriney, Stephen D" uniqKey="Meriney S" first="Stephen D." last="Meriney">Stephen D. Meriney</name>
<affiliation>
<nlm:aff id="A3">
<institution>Department of Neuroscience, University of Pittsburgh</institution>
,
<addr-line>Pittsburgh, PA 15260</addr-line>
,
<country>USA</country>
</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Schiavo, Giampietro" sort="Schiavo, Giampietro" uniqKey="Schiavo G" first="Giampietro" last="Schiavo">Giampietro Schiavo</name>
<affiliation>
<nlm:aff id="A7">
<institution>Molecular Neuropathobiology Laboratory, Cancer Research UK London Research Institute, Lincoln's Inn Fields Laboratories</institution>
,
<addr-line>London WC2A 3PX</addr-line>
,
<country>UK</country>
</nlm:aff>
</affiliation>
</author>
</analytic>
<series>
<title level="j">Journal of Cell Science</title>
<idno type="ISSN">0021-9533</idno>
<idno type="eISSN">1477-9137</idno>
<imprint>
<date when="2010">2010</date>
</imprint>
</series>
</biblStruct>
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<front>
<div type="abstract" xml:lang="en">
<p id="P1">Glycerotoxin (GLTx), a large neurotoxin isolated from the venom of the sea worm
<italic>Glycera convoluta</italic>
, promotes a long-lasting increase in spontaneous neurotransmitter release at the peripheral and central synapses by selective activation of Ca
<sub>v</sub>
2.2 channels. We found that GLTx stimulates the very high frequency, long-lasting (more than 10 hours) spontaneous release of acetylcholine by promoting nerve terminal Ca
<sup>2+</sup>
oscillations sensitive to the inhibitor ω-conotoxin GVIA at the amphibian neuromuscular junction. Although an estimate of the number of synaptic vesicles undergoing exocytosis largely exceeds the number of vesicles present in the motor nerve terminal, ultrastructural examination of GLTx-treated synapses revealed no significant change in the number of synaptic vesicles. However, we did detect the appearance of large pre-synaptic cisternae suggestive of bulk endocytosis. Using a combination of styryl dyes, photoconversion and horseradish peroxidase (HRP)-labeling electron microscopy, we demonstrate that GLTx upregulates presynaptic-vesicle recycling, which is likely to emanate from the limiting membrane of these large cisternae. Similar synaptic-vesicle recycling through bulk endocytosis also occurs from nerve terminals stimulated by high potassium. Our results suggest that this process might therefore contribute significantly to synaptic recycling under sustained levels of synaptic stimulation.</p>
</div>
</front>
</TEI>
<pmc article-type="research-article">
<pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<front>
<journal-meta>
<journal-id journal-id-type="nlm-ta">J Cell Sci</journal-id>
<journal-id journal-id-type="hwp">joces</journal-id>
<journal-id journal-id-type="publisher-id">jcs</journal-id>
<journal-title-group>
<journal-title>Journal of Cell Science</journal-title>
</journal-title-group>
<issn pub-type="ppub">0021-9533</issn>
<issn pub-type="epub">1477-9137</issn>
<publisher>
<publisher-name>Company of Biologists</publisher-name>
</publisher>
</journal-meta>
<article-meta>
<article-id pub-id-type="pmid">20215402</article-id>
<article-id pub-id-type="pmc">2844322</article-id>
<article-id pub-id-type="doi">10.1242/jcs.049296</article-id>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Research Articles</subject>
</subj-group>
</article-categories>
<title-group>
<article-title>Sustained synaptic-vesicle recycling by bulk endocytosis contributes to the maintenance of high-rate neurotransmitter release stimulated by glycerotoxin</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<name>
<surname>Meunier</surname>
<given-names>Frederic A.</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
<xref ref-type="corresp" rid="cor1">*</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Nguyen</surname>
<given-names>Tam H.</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Colasante</surname>
<given-names>Cesare</given-names>
</name>
<xref ref-type="aff" rid="A2">2</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Luo</surname>
<given-names>Fujun</given-names>
</name>
<xref ref-type="aff" rid="A3">3</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Sullivan</surname>
<given-names>Robert K. P.</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
<xref ref-type="aff" rid="A4">4</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Lavidis</surname>
<given-names>Nickolas A.</given-names>
</name>
<xref ref-type="aff" rid="A5">5</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Molgó</surname>
<given-names>Jordi</given-names>
</name>
<xref ref-type="aff" rid="A6">6</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Meriney</surname>
<given-names>Stephen D.</given-names>
</name>
<xref ref-type="aff" rid="A3">3</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Schiavo</surname>
<given-names>Giampietro</given-names>
</name>
<xref ref-type="aff" rid="A7">7</xref>
</contrib>
</contrib-group>
<aff id="A1">
<label>1</label>
<institution>Molecular Dynamics of Synaptic Function Laboratory, Queensland Brain Institute and School of Biomedical Sciences, The University of Queensland</institution>
,
<addr-line>Brisbane QLD 4072</addr-line>
,
<country>Australia</country>
</aff>
<aff id="A2">
<label>2</label>
<institution>Laboratorio de Fisiología de la Conducta, Facultad de Medicina, Universidad de Los Andes</institution>
,
<addr-line>Mérida 5101</addr-line>
,
<country>Venezuela</country>
</aff>
<aff id="A3">
<label>3</label>
<institution>Department of Neuroscience, University of Pittsburgh</institution>
,
<addr-line>Pittsburgh, PA 15260</addr-line>
,
<country>USA</country>
</aff>
<aff id="A4">
<label>4</label>
<institution>Centre for Microscopy and Microanalysis, The University of Queensland</institution>
,
<addr-line>Brisbane QLD 4072</addr-line>
,
<country>Australia</country>
</aff>
<aff id="A5">
<label>5</label>
<institution>School of Biomedical Sciences, The University of Queensland</institution>
,
<addr-line>Brisbane QLD 4072</addr-line>
,
<country>Australia</country>
</aff>
<aff id="A6">
<label>6</label>
<institution>CNRS, Institut de Neurobiologie Alfred Fessard – FRC2118, Laboratoire de Neurobiologie Cellulaire et Moléculaire – UPR9040</institution>
,
<addr-line>1 Avenue de la Terrasse, 91198 Gif sur Yvette</addr-line>
,
<country>France</country>
</aff>
<aff id="A7">
<label>7</label>
<institution>Molecular Neuropathobiology Laboratory, Cancer Research UK London Research Institute, Lincoln's Inn Fields Laboratories</institution>
,
<addr-line>London WC2A 3PX</addr-line>
,
<country>UK</country>
</aff>
<author-notes>
<corresp id="cor1">
<label>*</label>
Author for correspondence (
<email>f.meunier@uq.edu.au</email>
) </corresp>
</author-notes>
<pub-date pub-type="ppub">
<day>1</day>
<month>4</month>
<year>2010</year>
</pub-date>
<pub-date pub-type="epub">
<day>9</day>
<month>3</month>
<year>2010</year>
</pub-date>
<pub-date pub-type="pmc-release">
<day>1</day>
<month>4</month>
<year>2011</year>
</pub-date>
<pmc-comment> PMC Release delay is 12 months and 0 days and was based on the . </pmc-comment>
<volume>123</volume>
<issue>7</issue>
<fpage>1131</fpage>
<lpage>1140</lpage>
<history>
<date date-type="accepted">
<day>4</day>
<month>1</month>
<year>2010</year>
</date>
</history>
<permissions>
<copyright-statement>© 2010.</copyright-statement>
<copyright-year>2010</copyright-year>
</permissions>
<self-uri xlink:title="pdf" xlink:type="simple" xlink:href="1131.pdf"></self-uri>
<abstract>
<p id="P1">Glycerotoxin (GLTx), a large neurotoxin isolated from the venom of the sea worm
<italic>Glycera convoluta</italic>
, promotes a long-lasting increase in spontaneous neurotransmitter release at the peripheral and central synapses by selective activation of Ca
<sub>v</sub>
2.2 channels. We found that GLTx stimulates the very high frequency, long-lasting (more than 10 hours) spontaneous release of acetylcholine by promoting nerve terminal Ca
<sup>2+</sup>
oscillations sensitive to the inhibitor ω-conotoxin GVIA at the amphibian neuromuscular junction. Although an estimate of the number of synaptic vesicles undergoing exocytosis largely exceeds the number of vesicles present in the motor nerve terminal, ultrastructural examination of GLTx-treated synapses revealed no significant change in the number of synaptic vesicles. However, we did detect the appearance of large pre-synaptic cisternae suggestive of bulk endocytosis. Using a combination of styryl dyes, photoconversion and horseradish peroxidase (HRP)-labeling electron microscopy, we demonstrate that GLTx upregulates presynaptic-vesicle recycling, which is likely to emanate from the limiting membrane of these large cisternae. Similar synaptic-vesicle recycling through bulk endocytosis also occurs from nerve terminals stimulated by high potassium. Our results suggest that this process might therefore contribute significantly to synaptic recycling under sustained levels of synaptic stimulation.</p>
</abstract>
<kwd-group>
<kwd>Bulk endocytosis</kwd>
<kwd>Glycerotoxin</kwd>
<kwd>Synaptic-vesicle recycling</kwd>
<kwd>FM1-43</kwd>
<kwd>Photoconversion</kwd>
<kwd>Neurotransmitter release</kwd>
</kwd-group>
</article-meta>
</front>
</pmc>
</record>

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