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J. Troy Littleton. Buhl, Lauren Kaye Massachusetts Institute of Technology. Dept. of Brain and Cognitive Sciences. Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences 2011-08-18T19:13:28Z 2011-08-18T19:13:28Z 2011 2011 http://hdl.handle.net/1721.1/65285 744942533 Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Brain and Cognitive Sciences, 2011. Cataloged from PDF version of thesis. Includes bibliographical references. From yeast to humans, the fusion of vesicles with target membranes is driven by the formation of a parallel four-helix bundle of SNARE proteins that are present on both the vesicular (v-SNAREs) and target plasma membranes (t-SNAREs). The full zippering of this bundle is thought to provide the driving force for membrane fusion. At synapses, vesicle fusion is exquisitely regulated by Ca2+ such that neurotransmitter release can occur within 1 ms of an action potential reaching the presynaptic terminal. This feat implies the presence of both a Ca2+ sensor and a fusion clamp that prevents vesicles from fusing in the absence of Ca2+. The presynaptic Ca2+ sensor for synchronous vesicle release is widely accepted to be Synaptotagmin-1 (Syt1), and there is growing evidence that Complexin (Cpx), which binds to the SNARE complex with high affinity and 1:1 stoichiometry, can act as a vesicle fusion clamp. As suggested by its name, however, Cpx appears to play a more complex role in vesicle release, carrying out different functions in spontaneous vs. evoked fusion events. Here we show the Drosophila express at least two Cpx isoforms that differ in the C-terminus (Cpx7A and Cpx7B) and can be further regulated by RNA editing and phosphorylation. These isoforms show different effects on spontaneous vs. evoked neurotransmitter release, with Cpx7A being a better fusion clamp and Cpx7B being a better fusion promoter. In addition, these isoforms have different effects on synaptic growth, which may be linked to their effects on synaptic physiology. by Lauren Kaye Buhl. Ph.D. 150 p. eng Massachusetts Institute of Technology M.I.T. theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. See provided URL for inquiries about permission. http://dspace.mit.edu/handle/1721.1/7582 Brain and Cognitive Sciences. Synaptic structure and function at the Drosophila larval neuromuscular junction : a molecular analysis of complexin and radish Molecular analysis of complexin and radish Thesis application/pdf false Publication unknown unknown <Publication xmlns="https://www.openaire.eu/cerif-profile/1.1/" id="f4377e75-8881-468b-8f34-9892b821760a"> <Type xmlns="https://www.openaire.eu/cerif-profile/vocab/COAR_Publication_Types">http://purl.org/coar/resource_type/c_1843</Type> <Language>eng</Language> <Title>Synaptic structure and function at the Drosophila larval neuromuscular junction : a molecular analysis of complexin and radish</Title> <Subtitle>Molecular analysis of complexin and radish</Subtitle> <PublishedIn> <Publication> </Publication> </PublishedIn> <PublicationDate>2011</PublicationDate> <Authors> <Author> <DisplayName>Buhl, Lauren Kaye</DisplayName> <Affiliation> <OrgUnit> </OrgUnit> </Affiliation> </Author> </Authors> <Editors> </Editors> <Publishers> <Publisher> <DisplayName>Massachusetts Institute of Technology</DisplayName> <OrgUnit /> </Publisher> </Publishers> <License>http://dspace.mit.edu/handle/1721.1/7582</License> <Keyword>Brain and Cognitive Sciences.</Keyword> <Abstract>From yeast to humans, the fusion of vesicles with target membranes is driven by the formation of a parallel four-helix bundle of SNARE proteins that are present on both the vesicular (v-SNAREs) and target plasma membranes (t-SNAREs). The full zippering of this bundle is thought to provide the driving force for membrane fusion. At synapses, vesicle fusion is exquisitely regulated by Ca2+ such that neurotransmitter release can occur within 1 ms of an action potential reaching the presynaptic terminal. This feat implies the presence of both a Ca2+ sensor and a fusion clamp that prevents vesicles from fusing in the absence of Ca2+. The presynaptic Ca2+ sensor for synchronous vesicle release is widely accepted to be Synaptotagmin-1 (Syt1), and there is growing evidence that Complexin (Cpx), which binds to the SNARE complex with high affinity and 1:1 stoichiometry, can act as a vesicle fusion clamp. As suggested by its name, however, Cpx appears to play a more complex role in vesicle release, carrying out different functions in spontaneous vs. evoked fusion events. Here we show the Drosophila express at least two Cpx isoforms that differ in the C-terminus (Cpx7A and Cpx7B) and can be further regulated by RNA editing and phosphorylation. These isoforms show different effects on spontaneous vs. evoked neurotransmitter release, with Cpx7A being a better fusion clamp and Cpx7B being a better fusion promoter. In addition, these isoforms have different effects on synaptic growth, which may be linked to their effects on synaptic physiology.</Abstract> <Access xmlns="http://purl.org/coar/access_right" > </Access> </Publication>