SNAP-25 gene family members differentially support secretory vesicle fusion
Neuronal dense-core vesicles (DCVs) transport and secrete neuropeptides necessary for development, plasticity and survival, but little is known about their fusion mechanism. We show that -null mutant (SNAP-25 KO) neurons, previously shown to degenerate after 4 days (DIV), contain fewer DCVs and have...
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Veröffentlicht in: | Journal of cell science 2017-06, Vol.130 (11), p.1877-1889 |
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creator | Arora, Swati Saarloos, Ingrid Kooistra, Robbelien van de Bospoort, Rhea Verhage, Matthijs Toonen, Ruud F |
description | Neuronal dense-core vesicles (DCVs) transport and secrete neuropeptides necessary for development, plasticity and survival, but little is known about their fusion mechanism. We show that
-null mutant (SNAP-25 KO) neurons, previously shown to degenerate after 4 days
(DIV), contain fewer DCVs and have reduced DCV fusion probability in surviving neurons at DIV14. At DIV3, before degeneration, SNAP-25 KO neurons show normal DCV fusion, but one day later fusion is significantly reduced. To test if other SNAP homologs support DCV fusion, we expressed SNAP-23, SNAP-29 or SNAP-47 in SNAP-25 KO neurons. SNAP-23 and SNAP-29 rescued viability and supported DCV fusion in SNAP-25 KO neurons, but SNAP-23 did so more efficiently. SNAP-23 also rescued synaptic vesicle (SV) fusion while SNAP-29 did not. SNAP-47 failed to rescue viability and did not support DCV or SV fusion. These data demonstrate a developmental switch, in hippocampal neurons between DIV3 and DIV4, where DCV fusion becomes SNAP-25 dependent. Furthermore, SNAP-25 homologs support DCV and SV fusion and neuronal viability to variable extents - SNAP-23 most effectively, SNAP-29 less so and SNAP-47 ineffectively. |
doi_str_mv | 10.1242/jcs.201889 |
format | Article |
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-null mutant (SNAP-25 KO) neurons, previously shown to degenerate after 4 days
(DIV), contain fewer DCVs and have reduced DCV fusion probability in surviving neurons at DIV14. At DIV3, before degeneration, SNAP-25 KO neurons show normal DCV fusion, but one day later fusion is significantly reduced. To test if other SNAP homologs support DCV fusion, we expressed SNAP-23, SNAP-29 or SNAP-47 in SNAP-25 KO neurons. SNAP-23 and SNAP-29 rescued viability and supported DCV fusion in SNAP-25 KO neurons, but SNAP-23 did so more efficiently. SNAP-23 also rescued synaptic vesicle (SV) fusion while SNAP-29 did not. SNAP-47 failed to rescue viability and did not support DCV or SV fusion. These data demonstrate a developmental switch, in hippocampal neurons between DIV3 and DIV4, where DCV fusion becomes SNAP-25 dependent. Furthermore, SNAP-25 homologs support DCV and SV fusion and neuronal viability to variable extents - SNAP-23 most effectively, SNAP-29 less so and SNAP-47 ineffectively.</description><identifier>ISSN: 0021-9533</identifier><identifier>EISSN: 1477-9137</identifier><identifier>DOI: 10.1242/jcs.201889</identifier><identifier>PMID: 28404788</identifier><language>eng</language><publisher>England: The Company of Biologists Ltd</publisher><subject>Animals ; Biological Transport ; Cell Death - genetics ; Degeneration ; Dense core vesicles ; Developmental plasticity ; Embryo, Nonmammalian ; Exocytosis ; Gene Expression Regulation ; Genetic Complementation Test ; Hippocampus ; Hippocampus - metabolism ; Hippocampus - pathology ; Homology ; Membrane Fusion ; Mice ; Mice, Knockout ; Neurons ; Neurons - metabolism ; Neurons - pathology ; Neuropeptides ; Presynaptic Terminals - metabolism ; Presynaptic Terminals - pathology ; Primary Cell Culture ; Protein Isoforms - genetics ; Protein Isoforms - metabolism ; Qb-SNARE Proteins - genetics ; Qb-SNARE Proteins - metabolism ; Qc-SNARE Proteins - genetics ; Qc-SNARE Proteins - metabolism ; Secretory Vesicles - metabolism ; Secretory Vesicles - pathology ; SNAP-23 protein ; SNAP-25 protein ; Survival ; Synaptic Transmission ; Synaptosomal-Associated Protein 25 - deficiency ; Synaptosomal-Associated Protein 25 - genetics ; Vesicle fusion ; Viability</subject><ispartof>Journal of cell science, 2017-06, Vol.130 (11), p.1877-1889</ispartof><rights>2017. Published by The Company of Biologists Ltd.</rights><rights>Copyright The Company of Biologists Ltd Jun 1, 2017</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c384t-6fe1c97f4d4168bf0e5fba25bf8449d07d02b749bfc9c880ec2a051491b98cf63</citedby><cites>FETCH-LOGICAL-c384t-6fe1c97f4d4168bf0e5fba25bf8449d07d02b749bfc9c880ec2a051491b98cf63</cites><orcidid>0000-0002-9442-3359 ; 0000-0003-4576-8964 ; 0000-0002-2514-0216 ; 0000-0002-9900-4233</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,3678,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28404788$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Arora, Swati</creatorcontrib><creatorcontrib>Saarloos, Ingrid</creatorcontrib><creatorcontrib>Kooistra, Robbelien</creatorcontrib><creatorcontrib>van de Bospoort, Rhea</creatorcontrib><creatorcontrib>Verhage, Matthijs</creatorcontrib><creatorcontrib>Toonen, Ruud F</creatorcontrib><title>SNAP-25 gene family members differentially support secretory vesicle fusion</title><title>Journal of cell science</title><addtitle>J Cell Sci</addtitle><description>Neuronal dense-core vesicles (DCVs) transport and secrete neuropeptides necessary for development, plasticity and survival, but little is known about their fusion mechanism. We show that
-null mutant (SNAP-25 KO) neurons, previously shown to degenerate after 4 days
(DIV), contain fewer DCVs and have reduced DCV fusion probability in surviving neurons at DIV14. At DIV3, before degeneration, SNAP-25 KO neurons show normal DCV fusion, but one day later fusion is significantly reduced. To test if other SNAP homologs support DCV fusion, we expressed SNAP-23, SNAP-29 or SNAP-47 in SNAP-25 KO neurons. SNAP-23 and SNAP-29 rescued viability and supported DCV fusion in SNAP-25 KO neurons, but SNAP-23 did so more efficiently. SNAP-23 also rescued synaptic vesicle (SV) fusion while SNAP-29 did not. SNAP-47 failed to rescue viability and did not support DCV or SV fusion. These data demonstrate a developmental switch, in hippocampal neurons between DIV3 and DIV4, where DCV fusion becomes SNAP-25 dependent. Furthermore, SNAP-25 homologs support DCV and SV fusion and neuronal viability to variable extents - SNAP-23 most effectively, SNAP-29 less so and SNAP-47 ineffectively.</description><subject>Animals</subject><subject>Biological Transport</subject><subject>Cell Death - genetics</subject><subject>Degeneration</subject><subject>Dense core vesicles</subject><subject>Developmental plasticity</subject><subject>Embryo, Nonmammalian</subject><subject>Exocytosis</subject><subject>Gene Expression Regulation</subject><subject>Genetic Complementation Test</subject><subject>Hippocampus</subject><subject>Hippocampus - metabolism</subject><subject>Hippocampus - pathology</subject><subject>Homology</subject><subject>Membrane Fusion</subject><subject>Mice</subject><subject>Mice, Knockout</subject><subject>Neurons</subject><subject>Neurons - metabolism</subject><subject>Neurons - pathology</subject><subject>Neuropeptides</subject><subject>Presynaptic Terminals - metabolism</subject><subject>Presynaptic Terminals - pathology</subject><subject>Primary Cell Culture</subject><subject>Protein Isoforms - genetics</subject><subject>Protein Isoforms - metabolism</subject><subject>Qb-SNARE Proteins - genetics</subject><subject>Qb-SNARE Proteins - metabolism</subject><subject>Qc-SNARE Proteins - genetics</subject><subject>Qc-SNARE Proteins - metabolism</subject><subject>Secretory Vesicles - metabolism</subject><subject>Secretory Vesicles - pathology</subject><subject>SNAP-23 protein</subject><subject>SNAP-25 protein</subject><subject>Survival</subject><subject>Synaptic Transmission</subject><subject>Synaptosomal-Associated Protein 25 - deficiency</subject><subject>Synaptosomal-Associated Protein 25 - genetics</subject><subject>Vesicle fusion</subject><subject>Viability</subject><issn>0021-9533</issn><issn>1477-9137</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkU1LxDAQhoMo7rp68QdIwYsIXTNJ2iTHZfELFxXUc2nTiXTpl0kr7L83sqsHT15mYHjmhZmHkFOgc2CCXa2NnzMKSuk9MgUhZayBy30ypZRBrBPOJ-TI-zWlVDItD8mEKUGFVGpKHl4eF88xS6J3bDGyeVPVm6jBpkDno7KyFh22Q5XXYezHvu_cEHk0DofObaJP9JWpw97oq649Jgc2rz2e7PqMvN1cvy7v4tXT7f1ysYoNV2KIU4tgtLSiFJCqwlJMbJGzpLBKCF1SWVJWSKELa7RRiqJhOU1AaCi0MjblM3Kxze1d9zGiH7Km8gbrOm-xG30GGiAFnbJ_oEpJwYQAHdDzP-i6G10bDgmBigvOaCgzcrmljOu8d2iz3lVN7jYZ0OzbRhZsZFsbAT7bRY5Fg-Uv-vN-_gWvu4QB</recordid><startdate>20170601</startdate><enddate>20170601</enddate><creator>Arora, Swati</creator><creator>Saarloos, Ingrid</creator><creator>Kooistra, Robbelien</creator><creator>van de Bospoort, Rhea</creator><creator>Verhage, Matthijs</creator><creator>Toonen, Ruud F</creator><general>The Company of Biologists Ltd</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7TK</scope><scope>7TM</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-9442-3359</orcidid><orcidid>https://orcid.org/0000-0003-4576-8964</orcidid><orcidid>https://orcid.org/0000-0002-2514-0216</orcidid><orcidid>https://orcid.org/0000-0002-9900-4233</orcidid></search><sort><creationdate>20170601</creationdate><title>SNAP-25 gene family members differentially support secretory vesicle fusion</title><author>Arora, Swati ; 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We show that
-null mutant (SNAP-25 KO) neurons, previously shown to degenerate after 4 days
(DIV), contain fewer DCVs and have reduced DCV fusion probability in surviving neurons at DIV14. At DIV3, before degeneration, SNAP-25 KO neurons show normal DCV fusion, but one day later fusion is significantly reduced. To test if other SNAP homologs support DCV fusion, we expressed SNAP-23, SNAP-29 or SNAP-47 in SNAP-25 KO neurons. SNAP-23 and SNAP-29 rescued viability and supported DCV fusion in SNAP-25 KO neurons, but SNAP-23 did so more efficiently. SNAP-23 also rescued synaptic vesicle (SV) fusion while SNAP-29 did not. SNAP-47 failed to rescue viability and did not support DCV or SV fusion. These data demonstrate a developmental switch, in hippocampal neurons between DIV3 and DIV4, where DCV fusion becomes SNAP-25 dependent. Furthermore, SNAP-25 homologs support DCV and SV fusion and neuronal viability to variable extents - SNAP-23 most effectively, SNAP-29 less so and SNAP-47 ineffectively.</abstract><cop>England</cop><pub>The Company of Biologists Ltd</pub><pmid>28404788</pmid><doi>10.1242/jcs.201889</doi><tpages>13</tpages><orcidid>https://orcid.org/0000-0002-9442-3359</orcidid><orcidid>https://orcid.org/0000-0003-4576-8964</orcidid><orcidid>https://orcid.org/0000-0002-2514-0216</orcidid><orcidid>https://orcid.org/0000-0002-9900-4233</orcidid><oa>free_for_read</oa></addata></record> |
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source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection; Company of Biologists |
subjects | Animals Biological Transport Cell Death - genetics Degeneration Dense core vesicles Developmental plasticity Embryo, Nonmammalian Exocytosis Gene Expression Regulation Genetic Complementation Test Hippocampus Hippocampus - metabolism Hippocampus - pathology Homology Membrane Fusion Mice Mice, Knockout Neurons Neurons - metabolism Neurons - pathology Neuropeptides Presynaptic Terminals - metabolism Presynaptic Terminals - pathology Primary Cell Culture Protein Isoforms - genetics Protein Isoforms - metabolism Qb-SNARE Proteins - genetics Qb-SNARE Proteins - metabolism Qc-SNARE Proteins - genetics Qc-SNARE Proteins - metabolism Secretory Vesicles - metabolism Secretory Vesicles - pathology SNAP-23 protein SNAP-25 protein Survival Synaptic Transmission Synaptosomal-Associated Protein 25 - deficiency Synaptosomal-Associated Protein 25 - genetics Vesicle fusion Viability |
title | SNAP-25 gene family members differentially support secretory vesicle fusion |
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