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Regulation of quantal shape by Rab3A: evidence for a fusion pore-dependent mechanism
The function of Rab3A, a small GTPase located on synaptic vesicles, is not well understood. Studies in the Rab3A â/â mouse support a role in activity-dependent plasticity, but have not reported any effects on spontaneously occurring miniature synaptic currents, except that there is a decrease in...
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Published in: | The Journal of physiology 2008-08, Vol.586 (16), p.3949-3962 |
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creator | Wang, Xueyong Thiagarajan, Ramachandran Wang, Qingbo Tewolde, Teclemichael Rich, Mark M. Engisch, Kathrin L. |
description | The function of Rab3A, a small GTPase located on synaptic vesicles, is not well understood. Studies in the Rab3A â/â mouse support a role in activity-dependent plasticity, but have not reported any effects on spontaneously occurring miniature
synaptic currents, except that there is a decrease in resting frequency at the neuromuscular junction. Therefore we were surprised
to find an increase in the occurrence of mEPCs with abnormally long half-widths at the neuromuscular junctions of Rab3A â/â mice. The abnormal miniature endplate currents (mEPCs), which have significantly greater charge than the average mEPCs for
the same fibres, could arise from larger vesicles. However, the type of mEPC most increased in Rab3A â/â mice has a slow rise, which suggests it is not the result of full collapse fusion. To test if the slow mEPCs increased after
loss of Rab3A could be due to malfunctioning fusion pores, we used carbon fibre amperometry to record pre-spike feet, which
have been shown to correspond to the initial opening of a narrow fusion pore, in adrenal chromaffin cells of wild-type and
Rab3A â/â mice. We found that small amplitude pre-spike feet with abnormally long durations were increased in Rab3A â/â cells. The correspondence between mEPC and amperometric data supports our interpretation that slow rising, long half-width
mEPCs are caused by reduced diameter fusion pores that remain open longer. These data could be explained by a direct action
of Rab3A on the fusion pore, or by Rab3A-dependent control of vesicles with unusual fusion pore characteristics. |
doi_str_mv | 10.1113/jphysiol.2008.151191 |
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synaptic currents, except that there is a decrease in resting frequency at the neuromuscular junction. Therefore we were surprised
to find an increase in the occurrence of mEPCs with abnormally long half-widths at the neuromuscular junctions of Rab3A â/â mice. The abnormal miniature endplate currents (mEPCs), which have significantly greater charge than the average mEPCs for
the same fibres, could arise from larger vesicles. However, the type of mEPC most increased in Rab3A â/â mice has a slow rise, which suggests it is not the result of full collapse fusion. To test if the slow mEPCs increased after
loss of Rab3A could be due to malfunctioning fusion pores, we used carbon fibre amperometry to record pre-spike feet, which
have been shown to correspond to the initial opening of a narrow fusion pore, in adrenal chromaffin cells of wild-type and
Rab3A â/â mice. We found that small amplitude pre-spike feet with abnormally long durations were increased in Rab3A â/â cells. The correspondence between mEPC and amperometric data supports our interpretation that slow rising, long half-width
mEPCs are caused by reduced diameter fusion pores that remain open longer. These data could be explained by a direct action
of Rab3A on the fusion pore, or by Rab3A-dependent control of vesicles with unusual fusion pore characteristics.</description><identifier>ISSN: 0022-3751</identifier><identifier>EISSN: 1469-7793</identifier><identifier>DOI: 10.1113/jphysiol.2008.151191</identifier><identifier>PMID: 18591190</identifier><language>eng</language><publisher>Oxford, UK: The Physiological Society</publisher><subject>Animals ; Cells, Cultured ; Chromaffin Cells - physiology ; Excitatory Postsynaptic Potentials - physiology ; Ion Channel Gating - physiology ; Membrane Fusion - physiology ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Neuroscience ; Porosity ; rab3A GTP-Binding Protein - metabolism ; Synaptic Transmission - physiology ; Synaptic Vesicles - metabolism</subject><ispartof>The Journal of physiology, 2008-08, Vol.586 (16), p.3949-3962</ispartof><rights>2008 The Author. Journal compilation © 2008 The Physiological Society</rights><rights>2008 The Authors. Journal compilation © 2008 The Physiological Society 2008</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5211-1f27f17b80f30c01cf544fe194244a12c476cc63f31f155ddfdf3fc0eb7c2e133</citedby><cites>FETCH-LOGICAL-c5211-1f27f17b80f30c01cf544fe194244a12c476cc63f31f155ddfdf3fc0eb7c2e133</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1113%2Fjphysiol.2008.151191$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1113%2Fjphysiol.2008.151191$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>230,315,733,786,790,891,27957,27958,50923,51032,53827,53829</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18591190$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wang, Xueyong</creatorcontrib><creatorcontrib>Thiagarajan, Ramachandran</creatorcontrib><creatorcontrib>Wang, Qingbo</creatorcontrib><creatorcontrib>Tewolde, Teclemichael</creatorcontrib><creatorcontrib>Rich, Mark M.</creatorcontrib><creatorcontrib>Engisch, Kathrin L.</creatorcontrib><title>Regulation of quantal shape by Rab3A: evidence for a fusion pore-dependent mechanism</title><title>The Journal of physiology</title><addtitle>J Physiol</addtitle><description>The function of Rab3A, a small GTPase located on synaptic vesicles, is not well understood. Studies in the Rab3A â/â mouse support a role in activity-dependent plasticity, but have not reported any effects on spontaneously occurring miniature
synaptic currents, except that there is a decrease in resting frequency at the neuromuscular junction. Therefore we were surprised
to find an increase in the occurrence of mEPCs with abnormally long half-widths at the neuromuscular junctions of Rab3A â/â mice. The abnormal miniature endplate currents (mEPCs), which have significantly greater charge than the average mEPCs for
the same fibres, could arise from larger vesicles. However, the type of mEPC most increased in Rab3A â/â mice has a slow rise, which suggests it is not the result of full collapse fusion. To test if the slow mEPCs increased after
loss of Rab3A could be due to malfunctioning fusion pores, we used carbon fibre amperometry to record pre-spike feet, which
have been shown to correspond to the initial opening of a narrow fusion pore, in adrenal chromaffin cells of wild-type and
Rab3A â/â mice. We found that small amplitude pre-spike feet with abnormally long durations were increased in Rab3A â/â cells. The correspondence between mEPC and amperometric data supports our interpretation that slow rising, long half-width
mEPCs are caused by reduced diameter fusion pores that remain open longer. These data could be explained by a direct action
of Rab3A on the fusion pore, or by Rab3A-dependent control of vesicles with unusual fusion pore characteristics.</description><subject>Animals</subject><subject>Cells, Cultured</subject><subject>Chromaffin Cells - physiology</subject><subject>Excitatory Postsynaptic Potentials - physiology</subject><subject>Ion Channel Gating - physiology</subject><subject>Membrane Fusion - physiology</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Knockout</subject><subject>Neuroscience</subject><subject>Porosity</subject><subject>rab3A GTP-Binding Protein - metabolism</subject><subject>Synaptic Transmission - physiology</subject><subject>Synaptic Vesicles - metabolism</subject><issn>0022-3751</issn><issn>1469-7793</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><recordid>eNqNkU1v1DAQhi0EosvCP0AoJ6Qesnj8kcQckKoKCqgSqFrOluOMN66ycRonrfLvSZQtHyc4zWGe99WMHkJeA90BAH9329VT9KHZMUqLHUgABU_IBkSm0jxX_CnZUMpYynMJZ-RFjLeUAqdKPSdnUEg183RD9jd4GBsz-NAmwSV3o2kH0ySxNh0m5ZTcmJJfvE_w3lfYWkxc6BOTuDEugS70mFbYYTsvh-SItjatj8eX5JkzTcRXp7klPz593F9-Tq-_XX25vLhOrWQAKTiWO8jLgjpOLQXrpBAOQQkmhAFmRZ5Zm3HHwYGUVeUqx52lWOaWIXC-JR_W3m4sj1jZ-YjeNLrr_dH0kw7G6783ra_1IdxrJnmhoJgL3p4K-nA3Yhz00UeLTWNaDGPUmRI8F4L9E2RAZUGzpVGsoO1DjD26X9cA1Ys3_ehNL9706m2Ovfnzk9-hk6gZUCvw4Buc_qtU779-54vzLTlfs7U_1A--R73SMViPw6RlkWnINFdC8Z_AArfo</recordid><startdate>20080815</startdate><enddate>20080815</enddate><creator>Wang, Xueyong</creator><creator>Thiagarajan, Ramachandran</creator><creator>Wang, Qingbo</creator><creator>Tewolde, Teclemichael</creator><creator>Rich, Mark M.</creator><creator>Engisch, Kathrin L.</creator><general>The Physiological Society</general><general>Blackwell Publishing Ltd</general><general>Blackwell Science 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><scope>5PM</scope></search><sort><creationdate>20080815</creationdate><title>Regulation of quantal shape by Rab3A: evidence for a fusion pore-dependent mechanism</title><author>Wang, Xueyong ; Thiagarajan, Ramachandran ; Wang, Qingbo ; Tewolde, Teclemichael ; Rich, Mark M. ; Engisch, Kathrin L.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5211-1f27f17b80f30c01cf544fe194244a12c476cc63f31f155ddfdf3fc0eb7c2e133</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>Animals</topic><topic>Cells, Cultured</topic><topic>Chromaffin Cells - physiology</topic><topic>Excitatory Postsynaptic Potentials - physiology</topic><topic>Ion Channel Gating - physiology</topic><topic>Membrane Fusion - physiology</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Knockout</topic><topic>Neuroscience</topic><topic>Porosity</topic><topic>rab3A GTP-Binding Protein - metabolism</topic><topic>Synaptic Transmission - physiology</topic><topic>Synaptic Vesicles - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wang, Xueyong</creatorcontrib><creatorcontrib>Thiagarajan, Ramachandran</creatorcontrib><creatorcontrib>Wang, Qingbo</creatorcontrib><creatorcontrib>Tewolde, Teclemichael</creatorcontrib><creatorcontrib>Rich, Mark M.</creatorcontrib><creatorcontrib>Engisch, Kathrin L.</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><collection>PubMed Central (Full Participant titles)</collection><jtitle>The Journal of physiology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wang, Xueyong</au><au>Thiagarajan, Ramachandran</au><au>Wang, Qingbo</au><au>Tewolde, Teclemichael</au><au>Rich, Mark M.</au><au>Engisch, Kathrin L.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Regulation of quantal shape by Rab3A: evidence for a fusion pore-dependent mechanism</atitle><jtitle>The Journal of physiology</jtitle><addtitle>J Physiol</addtitle><date>2008-08-15</date><risdate>2008</risdate><volume>586</volume><issue>16</issue><spage>3949</spage><epage>3962</epage><pages>3949-3962</pages><issn>0022-3751</issn><eissn>1469-7793</eissn><notes>X. Wand and R. Thiagarajan contributed equally to this work.</notes><notes>ObjectType-Article-2</notes><notes>SourceType-Scholarly Journals-1</notes><notes>ObjectType-Feature-1</notes><notes>content type line 23</notes><notes>ObjectType-Article-1</notes><notes>ObjectType-Feature-2</notes><notes>Author's present address T. Tewolde: Neuroscience Institute, Morehouse School of Medicine, Atlanta, GA 30310, USA.</notes><abstract>The function of Rab3A, a small GTPase located on synaptic vesicles, is not well understood. Studies in the Rab3A â/â mouse support a role in activity-dependent plasticity, but have not reported any effects on spontaneously occurring miniature
synaptic currents, except that there is a decrease in resting frequency at the neuromuscular junction. Therefore we were surprised
to find an increase in the occurrence of mEPCs with abnormally long half-widths at the neuromuscular junctions of Rab3A â/â mice. The abnormal miniature endplate currents (mEPCs), which have significantly greater charge than the average mEPCs for
the same fibres, could arise from larger vesicles. However, the type of mEPC most increased in Rab3A â/â mice has a slow rise, which suggests it is not the result of full collapse fusion. To test if the slow mEPCs increased after
loss of Rab3A could be due to malfunctioning fusion pores, we used carbon fibre amperometry to record pre-spike feet, which
have been shown to correspond to the initial opening of a narrow fusion pore, in adrenal chromaffin cells of wild-type and
Rab3A â/â mice. We found that small amplitude pre-spike feet with abnormally long durations were increased in Rab3A â/â cells. The correspondence between mEPC and amperometric data supports our interpretation that slow rising, long half-width
mEPCs are caused by reduced diameter fusion pores that remain open longer. These data could be explained by a direct action
of Rab3A on the fusion pore, or by Rab3A-dependent control of vesicles with unusual fusion pore characteristics.</abstract><cop>Oxford, UK</cop><pub>The Physiological Society</pub><pmid>18591190</pmid><doi>10.1113/jphysiol.2008.151191</doi><tpages>14</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Animals Cells, Cultured Chromaffin Cells - physiology Excitatory Postsynaptic Potentials - physiology Ion Channel Gating - physiology Membrane Fusion - physiology Mice Mice, Inbred C57BL Mice, Knockout Neuroscience Porosity rab3A GTP-Binding Protein - metabolism Synaptic Transmission - physiology Synaptic Vesicles - metabolism |
title | Regulation of quantal shape by Rab3A: evidence for a fusion pore-dependent mechanism |
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