A Rho-related GTPase is involved in Ca(2+)-dependent neurotransmitter exocytosis
Rho, Rac, and Cdc42 monomeric GTPases are well known regulators of the actin cytoskeleton and phosphoinositide metabolism and have been implicated in hormone secretion in endocrine cells. Here, we examine their possible implication in Ca(2+)-dependent exocytosis of neurotransmitters. Using subcellul...
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| Veröffentlicht in: | The Journal of biological chemistry 2000-03, Vol.275 (11), p.7764 |
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| creator | Doussau, F Gasman, S Humeau, Y Vitiello, F Popoff, M Boquet, P Bader, M F Poulain, B |
| description | Rho, Rac, and Cdc42 monomeric GTPases are well known regulators of the actin cytoskeleton and phosphoinositide metabolism and have been implicated in hormone secretion in endocrine cells. Here, we examine their possible implication in Ca(2+)-dependent exocytosis of neurotransmitters. Using subcellular fractionation procedures, we found that RhoA, RhoB, Rac1, and Cdc42 are present in rat brain synaptosomes; however, only Rac1 was associated with highly purified synaptic vesicles. To determine the synaptic function of these GTPases, toxins that impair Rho-related proteins were microinjected into Aplysia neurons. We used lethal toxin from Clostridium sordellii, which inactivates Rac; toxin B from Clostridium difficile, which inactivates Rho, Rac, and Cdc42; and C3 exoenzyme from Clostridium botulinum and cytotoxic necrotizing factor 1 from Escherichia coli, which mainly affect Rho. Analysis of the toxin effects on evoked acetylcholine release revealed that a member of the Rho family, most likely Rac1, was implicated in the control of neurotransmitter release. Strikingly, blockage of acetylcholine release by lethal toxin and toxin B could be completely removed in |
| doi_str_mv | 10.1074/jbc.275.11.7764 |
| format | Article |
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Here, we examine their possible implication in Ca(2+)-dependent exocytosis of neurotransmitters. Using subcellular fractionation procedures, we found that RhoA, RhoB, Rac1, and Cdc42 are present in rat brain synaptosomes; however, only Rac1 was associated with highly purified synaptic vesicles. To determine the synaptic function of these GTPases, toxins that impair Rho-related proteins were microinjected into Aplysia neurons. We used lethal toxin from Clostridium sordellii, which inactivates Rac; toxin B from Clostridium difficile, which inactivates Rho, Rac, and Cdc42; and C3 exoenzyme from Clostridium botulinum and cytotoxic necrotizing factor 1 from Escherichia coli, which mainly affect Rho. Analysis of the toxin effects on evoked acetylcholine release revealed that a member of the Rho family, most likely Rac1, was implicated in the control of neurotransmitter release. Strikingly, blockage of acetylcholine release by lethal toxin and toxin B could be completely removed in <1 s by high frequency stimulation of nerve terminals. Further characterization of the inhibitory action produced by lethal toxin suggests that Rac1 protein regulates a late step in Ca(2+)-dependent neuroexocytosis.</description><identifier>ISSN: 0021-9258</identifier><identifier>DOI: 10.1074/jbc.275.11.7764</identifier><identifier>PMID: 10713089</identifier><language>eng</language><publisher>United States</publisher><subject>Acetylcholine - metabolism ; ADP Ribose Transferases - pharmacology ; Animals ; Aplysia ; Bacterial Toxins - pharmacology ; Botulinum Toxins ; Brain - metabolism ; Calcium - metabolism ; Cell Fractionation ; Clostridium ; Cytotoxins - pharmacology ; Electric Stimulation ; Escherichia coli Proteins ; Exocytosis - drug effects ; rac1 GTP-Binding Protein - metabolism ; Rats ; rho GTP-Binding Proteins - metabolism ; Synaptic Vesicles - metabolism</subject><ispartof>The Journal of biological chemistry, 2000-03, Vol.275 (11), p.7764</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27903,27904</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/10713089$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Doussau, F</creatorcontrib><creatorcontrib>Gasman, S</creatorcontrib><creatorcontrib>Humeau, Y</creatorcontrib><creatorcontrib>Vitiello, F</creatorcontrib><creatorcontrib>Popoff, M</creatorcontrib><creatorcontrib>Boquet, P</creatorcontrib><creatorcontrib>Bader, M F</creatorcontrib><creatorcontrib>Poulain, B</creatorcontrib><title>A Rho-related GTPase is involved in Ca(2+)-dependent neurotransmitter exocytosis</title><title>The Journal of biological chemistry</title><addtitle>J Biol Chem</addtitle><description>Rho, Rac, and Cdc42 monomeric GTPases are well known regulators of the actin cytoskeleton and phosphoinositide metabolism and have been implicated in hormone secretion in endocrine cells. Here, we examine their possible implication in Ca(2+)-dependent exocytosis of neurotransmitters. Using subcellular fractionation procedures, we found that RhoA, RhoB, Rac1, and Cdc42 are present in rat brain synaptosomes; however, only Rac1 was associated with highly purified synaptic vesicles. To determine the synaptic function of these GTPases, toxins that impair Rho-related proteins were microinjected into Aplysia neurons. We used lethal toxin from Clostridium sordellii, which inactivates Rac; toxin B from Clostridium difficile, which inactivates Rho, Rac, and Cdc42; and C3 exoenzyme from Clostridium botulinum and cytotoxic necrotizing factor 1 from Escherichia coli, which mainly affect Rho. Analysis of the toxin effects on evoked acetylcholine release revealed that a member of the Rho family, most likely Rac1, was implicated in the control of neurotransmitter release. Strikingly, blockage of acetylcholine release by lethal toxin and toxin B could be completely removed in <1 s by high frequency stimulation of nerve terminals. Further characterization of the inhibitory action produced by lethal toxin suggests that Rac1 protein regulates a late step in Ca(2+)-dependent neuroexocytosis.</description><subject>Acetylcholine - metabolism</subject><subject>ADP Ribose Transferases - pharmacology</subject><subject>Animals</subject><subject>Aplysia</subject><subject>Bacterial Toxins - pharmacology</subject><subject>Botulinum Toxins</subject><subject>Brain - metabolism</subject><subject>Calcium - metabolism</subject><subject>Cell Fractionation</subject><subject>Clostridium</subject><subject>Cytotoxins - pharmacology</subject><subject>Electric Stimulation</subject><subject>Escherichia coli Proteins</subject><subject>Exocytosis - drug effects</subject><subject>rac1 GTP-Binding Protein - metabolism</subject><subject>Rats</subject><subject>rho GTP-Binding Proteins - metabolism</subject><subject>Synaptic Vesicles - metabolism</subject><issn>0021-9258</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2000</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo1j89LwzAcxXNQ3JyevUmOirTmp0mPo-gUBg6Z55Em32BGm5YmG-6_t6C-y4P3eTx4CN1QUlKixOO-sSVTsqS0VOpJnKE5IYwWFZN6hi5T2pNJoqIXaDb1KSe6mqPNEn989cUIrcng8Gq7MQlwSDjEY98epyhEXJs79nBfOBggOogZRziMfR5NTF3IGUYM37095T6FdIXOvWkTXP_5An2-PG_r12L9vnqrl-tioIzlwoIQXgsppGSKs4o5pb3jTmvCLePO8kYJ7j2ptNYKNPXSWeclm6jwvuELdPu7OxyaDtxuGENnxtPu_xr_AUDJTm8</recordid><startdate>20000317</startdate><enddate>20000317</enddate><creator>Doussau, F</creator><creator>Gasman, S</creator><creator>Humeau, Y</creator><creator>Vitiello, F</creator><creator>Popoff, M</creator><creator>Boquet, P</creator><creator>Bader, M F</creator><creator>Poulain, B</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope></search><sort><creationdate>20000317</creationdate><title>A Rho-related GTPase is involved in Ca(2+)-dependent neurotransmitter exocytosis</title><author>Doussau, F ; Gasman, S ; Humeau, Y ; Vitiello, F ; Popoff, M ; Boquet, P ; Bader, M F ; Poulain, B</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-p122t-ce44f845455273292d78fd3d8803c23dc3b743ff098887e81f5dcdf523c24ffb3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2000</creationdate><topic>Acetylcholine - metabolism</topic><topic>ADP Ribose Transferases - pharmacology</topic><topic>Animals</topic><topic>Aplysia</topic><topic>Bacterial Toxins - pharmacology</topic><topic>Botulinum Toxins</topic><topic>Brain - metabolism</topic><topic>Calcium - metabolism</topic><topic>Cell Fractionation</topic><topic>Clostridium</topic><topic>Cytotoxins - pharmacology</topic><topic>Electric Stimulation</topic><topic>Escherichia coli Proteins</topic><topic>Exocytosis - drug effects</topic><topic>rac1 GTP-Binding Protein - metabolism</topic><topic>Rats</topic><topic>rho GTP-Binding Proteins - metabolism</topic><topic>Synaptic Vesicles - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Doussau, F</creatorcontrib><creatorcontrib>Gasman, S</creatorcontrib><creatorcontrib>Humeau, Y</creatorcontrib><creatorcontrib>Vitiello, F</creatorcontrib><creatorcontrib>Popoff, M</creatorcontrib><creatorcontrib>Boquet, P</creatorcontrib><creatorcontrib>Bader, M F</creatorcontrib><creatorcontrib>Poulain, B</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><jtitle>The Journal of biological chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Doussau, F</au><au>Gasman, S</au><au>Humeau, Y</au><au>Vitiello, F</au><au>Popoff, M</au><au>Boquet, P</au><au>Bader, M F</au><au>Poulain, B</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A Rho-related GTPase is involved in Ca(2+)-dependent neurotransmitter exocytosis</atitle><jtitle>The Journal of biological chemistry</jtitle><addtitle>J Biol Chem</addtitle><date>2000-03-17</date><risdate>2000</risdate><volume>275</volume><issue>11</issue><spage>7764</spage><pages>7764-</pages><issn>0021-9258</issn><abstract>Rho, Rac, and Cdc42 monomeric GTPases are well known regulators of the actin cytoskeleton and phosphoinositide metabolism and have been implicated in hormone secretion in endocrine cells. Here, we examine their possible implication in Ca(2+)-dependent exocytosis of neurotransmitters. Using subcellular fractionation procedures, we found that RhoA, RhoB, Rac1, and Cdc42 are present in rat brain synaptosomes; however, only Rac1 was associated with highly purified synaptic vesicles. To determine the synaptic function of these GTPases, toxins that impair Rho-related proteins were microinjected into Aplysia neurons. We used lethal toxin from Clostridium sordellii, which inactivates Rac; toxin B from Clostridium difficile, which inactivates Rho, Rac, and Cdc42; and C3 exoenzyme from Clostridium botulinum and cytotoxic necrotizing factor 1 from Escherichia coli, which mainly affect Rho. Analysis of the toxin effects on evoked acetylcholine release revealed that a member of the Rho family, most likely Rac1, was implicated in the control of neurotransmitter release. Strikingly, blockage of acetylcholine release by lethal toxin and toxin B could be completely removed in <1 s by high frequency stimulation of nerve terminals. Further characterization of the inhibitory action produced by lethal toxin suggests that Rac1 protein regulates a late step in Ca(2+)-dependent neuroexocytosis.</abstract><cop>United States</cop><pmid>10713089</pmid><doi>10.1074/jbc.275.11.7764</doi></addata></record> |
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| subjects | Acetylcholine - metabolism ADP Ribose Transferases - pharmacology Animals Aplysia Bacterial Toxins - pharmacology Botulinum Toxins Brain - metabolism Calcium - metabolism Cell Fractionation Clostridium Cytotoxins - pharmacology Electric Stimulation Escherichia coli Proteins Exocytosis - drug effects rac1 GTP-Binding Protein - metabolism Rats rho GTP-Binding Proteins - metabolism Synaptic Vesicles - metabolism |
| title | A Rho-related GTPase is involved in Ca(2+)-dependent neurotransmitter exocytosis |
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