Regulation of neuronal SNARE complexes by complexin and calcium(+2)-synaptotagmin

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dc.contributor.advisorMcNew, James A.en_US
dc.creatorDoneske, Blairen_US
dc.date.accessioned2009-06-03T19:51:50Zen_US
dc.date.available2009-06-03T19:51:50Zen_US
dc.date.issued2008en_US
dc.description.abstractSynaptic transmission relies on an exquisitely orchestrated series of protein-protein interactions that ultimately results in neurotransmitter release into the synaptic cleft. The final step in this reaction is membrane fusion of the synaptic vesicle with the presynaptic plasma membrane catalyzed by SNARE proteins. Several extrinsic protein factors impinge on the cycle of SNARE complex assembly to regulate vesicle release in space and time. These include general regulators such as the Rab family of GTPases and the Munc18/Sect (SM) proteins, as well as specific regulators of synaptic transmission including complexin and synaptotagmin. The interplay of these regulatory factors and their precise mechanisms of action remain an area of intense investigation. This work shows that fusion driven by a t-SNARE complex of Syntaxin1A/SNAP25 and the v-SNARE VAMP2, but not their yeast equivalents, is inhibited by complexin. Furthermore, inner leaflet mixing is strongly impaired relative to total lipid mixing indicating that inhibition by complexin arrests fusion at a hemifusion intermediate. When the calcium sensor synaptotagmin is added in the absence of calcium to the complexin-inhibited reaction, the arrest persists. However, when calcium is introduced, complexin inhibition is relieved and full fusion rapidly proceeds as evidenced by restoration of inner leaflet mixing. These results suggest that the combination of complexin and synaptotagmin provides a strong calcium-dependent clamp to inhibit full fusion at hemifusion until released by calcium influx.en_US
dc.format.extent98 p.en_US
dc.format.mimetypeapplication/pdfen_US
dc.identifier.callnoTHESIS BIOCHEM. 2009 DONESKEen_US
dc.identifier.citationDoneske, Blair. "Regulation of neuronal SNARE complexes by complexin and calcium(+2)-synaptotagmin." (2008) Diss., Rice University. <a href="https://hdl.handle.net/1911/22148">https://hdl.handle.net/1911/22148</a>.en_US
dc.identifier.urihttps://hdl.handle.net/1911/22148en_US
dc.language.isoengen_US
dc.rightsCopyright is held by the author, unless otherwise indicated. Permission to reuse, publish, or reproduce the work beyond the bounds of fair use or other exemptions to copyright law must be obtained from the copyright holder.en_US
dc.subjectNeurosciencesen_US
dc.subjectCell biologyen_US
dc.subjectBiochemistryen_US
dc.titleRegulation of neuronal SNARE complexes by complexin and calcium(+2)-synaptotagminen_US
dc.typeThesisen_US
dc.type.materialTexten_US
thesis.degree.departmentBiochemistry and Cell Biologyen_US
thesis.degree.disciplineNatural Sciencesen_US
thesis.degree.grantorRice Universityen_US
thesis.degree.levelDoctoralen_US
thesis.degree.nameDoctor of Philosophyen_US
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