A Novel Mechanism for Modulating Synaptic Gene Expression: Differential Localization of α-Dystrobrevin Transcripts in Skeletal Muscle
α-Dystrobrevin is a dystrophin-related and -associated protein that is involved in synapse maturation and is required for normal muscle function. There are three protein isoforms in skeletal muscle, α-dystrobrevin-1, -2, and -3 that are encoded by the single α-dystrobrevin gene. To understand the ro...
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| Veröffentlicht in: | Molecular and cellular neuroscience 2001-01, Vol.17 (1), p.127-140 |
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| creator | Newey, Sarah E. Gramolini, Anthony O. Wu, Jun Holzfeind, Paul Jasmin, Bernard J. Davies, Kay E. Blake, Derek J. |
| description | α-Dystrobrevin is a dystrophin-related and -associated protein that is involved in synapse maturation and is required for normal muscle function. There are three protein isoforms in skeletal muscle, α-dystrobrevin-1, -2, and -3 that are encoded by the single α-dystrobrevin gene. To understand the role of these proteins in muscle we have investigated the localisation and transcript distribution of the different α-dystrobrevin isoforms. α-Dystrobrevin-1 and -2 are concentrated at the neuromuscular junction and are both recruited into agrin-induced acetylcholine receptor clusters in cultured myotubes. We also demonstrate that all α-dystrobrevin mRNAs are transcribed from a single promoter in skeletal muscle. However, only transcripts encoding α-dystrobrevin-1 are preferentially accumulated at postsynaptic sites. These data suggest that the synaptic accumulation of α-dystrobrevin-1 mRNA occurs posttranscriptionally, identifying a novel mechanism for synaptic gene expression. Taken together, these results indicate that different isoforms possess distinct roles in synapse formation and possibly in the pathogenesis of muscular dystrophy. |
| doi_str_mv | 10.1006/mcne.2000.0918 |
| format | Article |
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There are three protein isoforms in skeletal muscle, α-dystrobrevin-1, -2, and -3 that are encoded by the single α-dystrobrevin gene. To understand the role of these proteins in muscle we have investigated the localisation and transcript distribution of the different α-dystrobrevin isoforms. α-Dystrobrevin-1 and -2 are concentrated at the neuromuscular junction and are both recruited into agrin-induced acetylcholine receptor clusters in cultured myotubes. We also demonstrate that all α-dystrobrevin mRNAs are transcribed from a single promoter in skeletal muscle. However, only transcripts encoding α-dystrobrevin-1 are preferentially accumulated at postsynaptic sites. These data suggest that the synaptic accumulation of α-dystrobrevin-1 mRNA occurs posttranscriptionally, identifying a novel mechanism for synaptic gene expression. Taken together, these results indicate that different isoforms possess distinct roles in synapse formation and possibly in the pathogenesis of muscular dystrophy.</description><identifier>ISSN: 1044-7431</identifier><identifier>EISSN: 1095-9327</identifier><identifier>DOI: 10.1006/mcne.2000.0918</identifier><identifier>PMID: 11161474</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>a-Dystrobrevin ; Agrin - pharmacology ; Animals ; Cell Line ; Cytoskeletal Proteins - genetics ; Cytoskeletal Proteins - metabolism ; Dystrophin-Associated Proteins ; Gene Expression Regulation - physiology ; Membrane Proteins - genetics ; Membrane Proteins - metabolism ; Mice ; Mice, Inbred C57BL ; Mice, Inbred mdx ; Muscle, Skeletal - cytology ; Muscle, Skeletal - drug effects ; Muscle, Skeletal - metabolism ; Promoter Regions, Genetic ; Protein Isoforms - genetics ; Protein Isoforms - metabolism ; Receptor Aggregation - drug effects ; Receptors, Cholinergic - drug effects ; Receptors, Cholinergic - metabolism ; RNA, Messenger - metabolism ; Synapses - genetics ; Synapses - metabolism</subject><ispartof>Molecular and cellular neuroscience, 2001-01, Vol.17 (1), p.127-140</ispartof><rights>2001 Academic Press</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c371t-78582ebe8ba0b60c06b481dd2c7cc281ce00acfacac525980ac2ca8435559a903</citedby><cites>FETCH-LOGICAL-c371t-78582ebe8ba0b60c06b481dd2c7cc281ce00acfacac525980ac2ca8435559a903</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1006/mcne.2000.0918$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,777,781,3537,27905,27906,45976</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11161474$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Newey, Sarah E.</creatorcontrib><creatorcontrib>Gramolini, Anthony O.</creatorcontrib><creatorcontrib>Wu, Jun</creatorcontrib><creatorcontrib>Holzfeind, Paul</creatorcontrib><creatorcontrib>Jasmin, Bernard J.</creatorcontrib><creatorcontrib>Davies, Kay E.</creatorcontrib><creatorcontrib>Blake, Derek J.</creatorcontrib><title>A Novel Mechanism for Modulating Synaptic Gene Expression: Differential Localization of α-Dystrobrevin Transcripts in Skeletal Muscle</title><title>Molecular and cellular neuroscience</title><addtitle>Mol Cell Neurosci</addtitle><description>α-Dystrobrevin is a dystrophin-related and -associated protein that is involved in synapse maturation and is required for normal muscle function. There are three protein isoforms in skeletal muscle, α-dystrobrevin-1, -2, and -3 that are encoded by the single α-dystrobrevin gene. To understand the role of these proteins in muscle we have investigated the localisation and transcript distribution of the different α-dystrobrevin isoforms. α-Dystrobrevin-1 and -2 are concentrated at the neuromuscular junction and are both recruited into agrin-induced acetylcholine receptor clusters in cultured myotubes. We also demonstrate that all α-dystrobrevin mRNAs are transcribed from a single promoter in skeletal muscle. However, only transcripts encoding α-dystrobrevin-1 are preferentially accumulated at postsynaptic sites. These data suggest that the synaptic accumulation of α-dystrobrevin-1 mRNA occurs posttranscriptionally, identifying a novel mechanism for synaptic gene expression. Taken together, these results indicate that different isoforms possess distinct roles in synapse formation and possibly in the pathogenesis of muscular dystrophy.</description><subject>a-Dystrobrevin</subject><subject>Agrin - pharmacology</subject><subject>Animals</subject><subject>Cell Line</subject><subject>Cytoskeletal Proteins - genetics</subject><subject>Cytoskeletal Proteins - metabolism</subject><subject>Dystrophin-Associated Proteins</subject><subject>Gene Expression Regulation - physiology</subject><subject>Membrane Proteins - genetics</subject><subject>Membrane Proteins - metabolism</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Inbred mdx</subject><subject>Muscle, Skeletal - cytology</subject><subject>Muscle, Skeletal - drug effects</subject><subject>Muscle, Skeletal - metabolism</subject><subject>Promoter Regions, Genetic</subject><subject>Protein Isoforms - genetics</subject><subject>Protein Isoforms - metabolism</subject><subject>Receptor Aggregation - drug effects</subject><subject>Receptors, Cholinergic - drug effects</subject><subject>Receptors, Cholinergic - metabolism</subject><subject>RNA, Messenger - metabolism</subject><subject>Synapses - genetics</subject><subject>Synapses - metabolism</subject><issn>1044-7431</issn><issn>1095-9327</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2001</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkcFu1DAQhiMEoqVw5Yh84pbFTuLY4Va1pSDtwqHlbDmTCRgcO9jOiuUBeB9ehGfC0a7ECXGaGen7_8N8RfGc0Q2jtH01gcNNRSnd0I7JB8U5ox0vu7oSD9e9aUrR1OyseBLjl0zxqqsfF2eMsZY1ojkvfl6S936PluwQPmtn4kRGH8jOD4vVybhP5O7g9JwMkFt0SG6-zwFjNN69JtdmHDGgS0ZbsvWgrfmRM94RP5Lfv8rrQ0zB9wH3xpH7oF2EYOYUST7vvqLFlHO7JYLFp8WjUduIz07zovj45ub-6m25_XD77upyW0ItWCqF5LLCHmWvad9SoG3fSDYMFQiASjJASjWMGjTwincyHxVo2dSc8053tL4oXh575-C_LRiTmkwEtFY79EtUgra1rIX4L8iEzI9ueAY3RxCCjzHgqOZgJh0OilG1KlKrIrUqUquiHHhxal76CYe_-MlJBuQRwPyIvcGgIhh0gIMJCEkN3vyr-w8e86MT</recordid><startdate>200101</startdate><enddate>200101</enddate><creator>Newey, Sarah E.</creator><creator>Gramolini, Anthony O.</creator><creator>Wu, Jun</creator><creator>Holzfeind, Paul</creator><creator>Jasmin, Bernard J.</creator><creator>Davies, Kay E.</creator><creator>Blake, Derek J.</creator><general>Elsevier Inc</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>7TK</scope><scope>7X8</scope></search><sort><creationdate>200101</creationdate><title>A Novel Mechanism for Modulating Synaptic Gene Expression: Differential Localization of α-Dystrobrevin Transcripts in Skeletal Muscle</title><author>Newey, Sarah E. ; Gramolini, Anthony O. ; Wu, Jun ; Holzfeind, Paul ; Jasmin, Bernard J. ; Davies, Kay E. ; Blake, Derek J.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c371t-78582ebe8ba0b60c06b481dd2c7cc281ce00acfacac525980ac2ca8435559a903</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2001</creationdate><topic>a-Dystrobrevin</topic><topic>Agrin - pharmacology</topic><topic>Animals</topic><topic>Cell Line</topic><topic>Cytoskeletal Proteins - genetics</topic><topic>Cytoskeletal Proteins - metabolism</topic><topic>Dystrophin-Associated Proteins</topic><topic>Gene Expression Regulation - physiology</topic><topic>Membrane Proteins - genetics</topic><topic>Membrane Proteins - metabolism</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Inbred mdx</topic><topic>Muscle, Skeletal - cytology</topic><topic>Muscle, Skeletal - drug effects</topic><topic>Muscle, Skeletal - metabolism</topic><topic>Promoter Regions, Genetic</topic><topic>Protein Isoforms - genetics</topic><topic>Protein Isoforms - metabolism</topic><topic>Receptor Aggregation - drug effects</topic><topic>Receptors, Cholinergic - drug effects</topic><topic>Receptors, Cholinergic - metabolism</topic><topic>RNA, Messenger - metabolism</topic><topic>Synapses - genetics</topic><topic>Synapses - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Newey, Sarah E.</creatorcontrib><creatorcontrib>Gramolini, Anthony O.</creatorcontrib><creatorcontrib>Wu, Jun</creatorcontrib><creatorcontrib>Holzfeind, Paul</creatorcontrib><creatorcontrib>Jasmin, Bernard J.</creatorcontrib><creatorcontrib>Davies, Kay E.</creatorcontrib><creatorcontrib>Blake, Derek J.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Neurosciences Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Molecular and cellular neuroscience</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Newey, Sarah E.</au><au>Gramolini, Anthony O.</au><au>Wu, Jun</au><au>Holzfeind, Paul</au><au>Jasmin, Bernard J.</au><au>Davies, Kay E.</au><au>Blake, Derek J.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A Novel Mechanism for Modulating Synaptic Gene Expression: Differential Localization of α-Dystrobrevin Transcripts in Skeletal Muscle</atitle><jtitle>Molecular and cellular neuroscience</jtitle><addtitle>Mol Cell Neurosci</addtitle><date>2001-01</date><risdate>2001</risdate><volume>17</volume><issue>1</issue><spage>127</spage><epage>140</epage><pages>127-140</pages><issn>1044-7431</issn><eissn>1095-9327</eissn><abstract>α-Dystrobrevin is a dystrophin-related and -associated protein that is involved in synapse maturation and is required for normal muscle function. There are three protein isoforms in skeletal muscle, α-dystrobrevin-1, -2, and -3 that are encoded by the single α-dystrobrevin gene. To understand the role of these proteins in muscle we have investigated the localisation and transcript distribution of the different α-dystrobrevin isoforms. α-Dystrobrevin-1 and -2 are concentrated at the neuromuscular junction and are both recruited into agrin-induced acetylcholine receptor clusters in cultured myotubes. We also demonstrate that all α-dystrobrevin mRNAs are transcribed from a single promoter in skeletal muscle. However, only transcripts encoding α-dystrobrevin-1 are preferentially accumulated at postsynaptic sites. These data suggest that the synaptic accumulation of α-dystrobrevin-1 mRNA occurs posttranscriptionally, identifying a novel mechanism for synaptic gene expression. 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| subjects | a-Dystrobrevin Agrin - pharmacology Animals Cell Line Cytoskeletal Proteins - genetics Cytoskeletal Proteins - metabolism Dystrophin-Associated Proteins Gene Expression Regulation - physiology Membrane Proteins - genetics Membrane Proteins - metabolism Mice Mice, Inbred C57BL Mice, Inbred mdx Muscle, Skeletal - cytology Muscle, Skeletal - drug effects Muscle, Skeletal - metabolism Promoter Regions, Genetic Protein Isoforms - genetics Protein Isoforms - metabolism Receptor Aggregation - drug effects Receptors, Cholinergic - drug effects Receptors, Cholinergic - metabolism RNA, Messenger - metabolism Synapses - genetics Synapses - metabolism |
| title | A Novel Mechanism for Modulating Synaptic Gene Expression: Differential Localization of α-Dystrobrevin Transcripts in Skeletal Muscle |
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