β Phorbol Ester- and Diacylglycerol-Induced Augmentation of Transmitter Release Is Mediated by Munc13s and Not by PKCs
Munc13-1 is a presynaptic protein with an essential role in synaptic vesicle priming. It contains a diacylglycerol (DAG)/β phorbol ester binding C 1 domain and is a potential target of the DAG second messenger pathway that may act in parallel with PKCs. Using genetically modified mice that express a...
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| Veröffentlicht in: | Cell 2002-01, Vol.108 (1), p.121-133 |
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| container_title | Cell |
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| creator | Rhee, Jeong-Seop Betz, Andrea Pyott, Sonja Reim, Kerstin Varoqueaux, Frederique Augustin, Iris Hesse, Dörte Südhof, Thomas C. Takahashi, Masami Rosenmund, Christian Brose, Nils |
| description | Munc13-1 is a presynaptic protein with an essential role in synaptic vesicle priming. It contains a diacylglycerol (DAG)/β phorbol ester binding C
1 domain and is a potential target of the DAG second messenger pathway that may act in parallel with PKCs. Using genetically modified mice that express a DAG/β phorbol ester binding-deficient Munc13-1
H567K variant instead of the wild-type protein, we determined the relative contribution of PKCs and Munc13-1 to DAG/β phorbol ester-dependent regulation of neurotransmitter release. We show that Munc13s are the main presynaptic DAG/β phorbol ester receptors in hippocampal neurons. Modulation of Munc13-1 activity by second messengers via the DAG/β phorbol ester binding C
1 domain is essential for use-dependent alterations of synaptic efficacy and survival. |
| doi_str_mv | 10.1016/S0092-8674(01)00635-3 |
| format | Article |
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H567K variant instead of the wild-type protein, we determined the relative contribution of PKCs and Munc13-1 to DAG/β phorbol ester-dependent regulation of neurotransmitter release. We show that Munc13s are the main presynaptic DAG/β phorbol ester receptors in hippocampal neurons. Modulation of Munc13-1 activity by second messengers via the DAG/β phorbol ester binding C
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H567K variant instead of the wild-type protein, we determined the relative contribution of PKCs and Munc13-1 to DAG/β phorbol ester-dependent regulation of neurotransmitter release. We show that Munc13s are the main presynaptic DAG/β phorbol ester receptors in hippocampal neurons. Modulation of Munc13-1 activity by second messengers via the DAG/β phorbol ester binding C
1 domain is essential for use-dependent alterations of synaptic efficacy and survival.</description><subject>Amino Acid Sequence</subject><subject>Animals</subject><subject>Base Sequence</subject><subject>Binding Sites - genetics</subject><subject>Cells, Cultured</subject><subject>diacylglycerol</subject><subject>Diglycerides - metabolism</subject><subject>Gene Expression - physiology</subject><subject>Hippocampus - cytology</subject><subject>Intracellular Signaling Peptides and Proteins</subject><subject>Mice</subject><subject>Molecular Sequence Data</subject><subject>Munc13-1 protein</subject><subject>Mutagenesis - physiology</subject><subject>Nerve Tissue Proteins - genetics</subject><subject>Nerve Tissue Proteins - metabolism</subject><subject>Neurons - cytology</subject><subject>Phorbol Esters - pharmacology</subject><subject>Point Mutation - physiology</subject><subject>Protein Kinase C - genetics</subject><subject>Protein Kinase C - metabolism</subject><subject>Synapses - enzymology</subject><subject>Synaptic Transmission - drug effects</subject><subject>Synaptic Transmission - physiology</subject><issn>0092-8674</issn><issn>1097-4172</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2002</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkMtO3TAQhq2qqBygjwDyqoJFwPckqwodbkdc1dK15TgT6iqJwXZA57V4EJ6JnIvKktVIo-__R_MhtEvJISVUHf0mpGRZoXKxT-gBIYrLjH9BE0rKPBM0Z1_R5D-yibZi_EcIKaSU39AmpXnJOFMT9PL2iu_--lD5Fp_GBCHDpq_xiTN23j60cwvBt9msrwcLNT4eHjrok0nO99g3-D6YPnYujTn8C1owEfAs4muonUkjX83x9dBbyuOy9canxeruchp30EZj2gjf13Mb_Tk7vZ9eZFe357Pp8VVmRclTVjArBHBpBC9Vnld1I0pLFLXGiFoIRUuQklUSrGSsMaRSlWkKWRWKNszwnG-jH6vex-CfBohJdy5aaFvTgx-ipgVTbCwaQbkCbfAxBmj0Y3CdCXNNiV4Y10vjeqFTE6qXxjUfc3vrA0PVQf2RWisegZ8rAMY3nx0EHa2DftTpAtika-8-OfEOJVmQqA</recordid><startdate>20020111</startdate><enddate>20020111</enddate><creator>Rhee, Jeong-Seop</creator><creator>Betz, Andrea</creator><creator>Pyott, Sonja</creator><creator>Reim, Kerstin</creator><creator>Varoqueaux, Frederique</creator><creator>Augustin, Iris</creator><creator>Hesse, Dörte</creator><creator>Südhof, Thomas C.</creator><creator>Takahashi, Masami</creator><creator>Rosenmund, Christian</creator><creator>Brose, Nils</creator><general>Elsevier Inc</general><scope>6I.</scope><scope>AAFTH</scope><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></search><sort><creationdate>20020111</creationdate><title>β Phorbol Ester- and Diacylglycerol-Induced Augmentation of Transmitter Release Is Mediated by Munc13s and Not by PKCs</title><author>Rhee, Jeong-Seop ; Betz, Andrea ; Pyott, Sonja ; Reim, Kerstin ; Varoqueaux, Frederique ; Augustin, Iris ; Hesse, Dörte ; Südhof, Thomas C. ; Takahashi, Masami ; Rosenmund, Christian ; Brose, Nils</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c493t-82c44e35a439677bdf49c061caa4d44619e552b5ec522fa0b6baf85b861f2a373</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2002</creationdate><topic>Amino Acid Sequence</topic><topic>Animals</topic><topic>Base Sequence</topic><topic>Binding Sites - genetics</topic><topic>Cells, Cultured</topic><topic>diacylglycerol</topic><topic>Diglycerides - metabolism</topic><topic>Gene Expression - physiology</topic><topic>Hippocampus - cytology</topic><topic>Intracellular Signaling Peptides and Proteins</topic><topic>Mice</topic><topic>Molecular Sequence Data</topic><topic>Munc13-1 protein</topic><topic>Mutagenesis - physiology</topic><topic>Nerve Tissue Proteins - genetics</topic><topic>Nerve Tissue Proteins - metabolism</topic><topic>Neurons - cytology</topic><topic>Phorbol Esters - pharmacology</topic><topic>Point Mutation - physiology</topic><topic>Protein Kinase C - genetics</topic><topic>Protein Kinase C - metabolism</topic><topic>Synapses - enzymology</topic><topic>Synaptic Transmission - drug effects</topic><topic>Synaptic Transmission - physiology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Rhee, Jeong-Seop</creatorcontrib><creatorcontrib>Betz, Andrea</creatorcontrib><creatorcontrib>Pyott, Sonja</creatorcontrib><creatorcontrib>Reim, Kerstin</creatorcontrib><creatorcontrib>Varoqueaux, Frederique</creatorcontrib><creatorcontrib>Augustin, Iris</creatorcontrib><creatorcontrib>Hesse, Dörte</creatorcontrib><creatorcontrib>Südhof, Thomas C.</creatorcontrib><creatorcontrib>Takahashi, Masami</creatorcontrib><creatorcontrib>Rosenmund, Christian</creatorcontrib><creatorcontrib>Brose, Nils</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><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><jtitle>Cell</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Rhee, Jeong-Seop</au><au>Betz, Andrea</au><au>Pyott, Sonja</au><au>Reim, Kerstin</au><au>Varoqueaux, Frederique</au><au>Augustin, Iris</au><au>Hesse, Dörte</au><au>Südhof, Thomas C.</au><au>Takahashi, Masami</au><au>Rosenmund, Christian</au><au>Brose, Nils</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>β Phorbol Ester- and Diacylglycerol-Induced Augmentation of Transmitter Release Is Mediated by Munc13s and Not by PKCs</atitle><jtitle>Cell</jtitle><addtitle>Cell</addtitle><date>2002-01-11</date><risdate>2002</risdate><volume>108</volume><issue>1</issue><spage>121</spage><epage>133</epage><pages>121-133</pages><issn>0092-8674</issn><eissn>1097-4172</eissn><abstract>Munc13-1 is a presynaptic protein with an essential role in synaptic vesicle priming. 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| subjects | Amino Acid Sequence Animals Base Sequence Binding Sites - genetics Cells, Cultured diacylglycerol Diglycerides - metabolism Gene Expression - physiology Hippocampus - cytology Intracellular Signaling Peptides and Proteins Mice Molecular Sequence Data Munc13-1 protein Mutagenesis - physiology Nerve Tissue Proteins - genetics Nerve Tissue Proteins - metabolism Neurons - cytology Phorbol Esters - pharmacology Point Mutation - physiology Protein Kinase C - genetics Protein Kinase C - metabolism Synapses - enzymology Synaptic Transmission - drug effects Synaptic Transmission - physiology |
| title | β Phorbol Ester- and Diacylglycerol-Induced Augmentation of Transmitter Release Is Mediated by Munc13s and Not by PKCs |
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