Functional Studies of SNAP-25 using a knock-out and rescue approach

Delgado Martínez, Ignacio

dc.contributor.advisor	Sørensen, Jakob Dr.	de
dc.contributor.author	Delgado Martínez, Ignacio	de
dc.date.accessioned	2006-11-01T06:48:32Z	de
dc.date.accessioned	2013-01-18T14:28:46Z	de
dc.date.available	2013-01-30T23:51:09Z	de
dc.date.issued	2006-11-01	de
dc.identifier.uri	http://hdl.handle.net/11858/00-1735-0000-0006-B363-0	de
dc.identifier.uri	http://dx.doi.org/10.53846/goediss-3299
dc.format.mimetype	application/pdf	de
dc.language.iso	eng	de
dc.rights.uri	http://webdoc.sub.gwdg.de/diss/copyr_diss.html	de
dc.title	Functional Studies of SNAP-25 using a knock-out and rescue approach	de
dc.type	doctoralThesis	de
dc.contributor.referee	Sørensen, Jakob Dr.	de
dc.date.examination	2006-10-18	de
dc.subject.dnb	570 Biowissenschaften	de
dc.subject.dnb	Biologie	de
dc.description.abstracteng	The neuronal SNARE complex, consisting of SNAP-25, synaptobrevin and syntaxin, is required for presynaptic exocytosis of neurotransmitter-filled vesicles during synaptic transmission. However the SNARE complex undertakes neuronal developmental roles as well. SNAP-25 has been involved in vesicular fusion during axonal outgrowth, synaptic formation and trafficking of glutamate receptors. Its expression is developmentally regulated by alternative splicing from SNAP-25a to SNAP-25b. In GABAergic neurons, SNAP-25 seems to be replaced by SNAP-23, a ubiquitousSNAP-25 homologue, after synaptogenesis. Deletion of SNAP-25 compromises neuronal survival in culture, impeding detailed functional studies. Here, I overcame this difficulty by reintroducing SNAP-25a, SNAP-25b or SNAP-23 using the long-term expression lentiviral system in culture neurons from Snap25 null mice and I was able to dissect the main functions of SNAP-25. I found that that SNAP-25 deficient cultured neurons presented impaired arborization and severe reduction in viability as well as complete arrest of evoked release and reduction in the amplitude and frequency of the spontaneous events. Expression of the SNAP-25 homologues restored neuronal survival, arborization and the properties of spontaneous release. In addition, it rescued evoked release, in both glutamatergic and GABAergic neurons, although SNAP-23 was found to support exclusively asynchronous release. SNAP-25b was superior to SNAP-25a in vesicle priming, which would produce larger releasable pools after synaptic maturation. My results revealed SNAP-25 as key component for neuronal survival and outgrowth, regulation of the synchronous and asynchronous release and spontaneous activity and demonstrate a hierarchical ability of the SNAP-25 homologues to support neuronal function.	de
dc.contributor.coReferee	Jahn, Reinhard Prof. Dr.	de
dc.contributor.thirdReferee	Schild, Detlev Prof. Dr.	de
dc.subject.topic	Molecular Biology & Neurosciences Program	de
dc.subject.eng	Lentivirus	de
dc.subject.eng	autaptic culture	de
dc.subject.eng	neurite outgrowth	de
dc.subject.eng	spontaneous release	de
dc.subject.eng	synchronous release	de
dc.subject.bk	42.13	de
dc.subject.bk	42.17	de
dc.subject.bk	44.37	de
dc.subject.bk	44.90	de
dc.identifier.urn	urn:nbn:de:gbv:7-webdoc-1321-1	de
dc.identifier.purl	webdoc-1321	de
dc.affiliation.institute	Göttinger Graduiertenschule für Neurowissenschaften und molekulare Biowissenschaften (GGNB)	de
dc.subject.gokfull	WCK 000: Bioelektrizität und Biomagnetismus {Biophysik}	de
dc.subject.gokfull	MED 283: Molekularbiologie {Medizin}	de
dc.subject.gokfull	MED 311: Physiologie {Medizin}	de
dc.subject.gokfull	MED 531: Neuroanatomie	de
dc.subject.gokfull	Neurophysiologie	de
dc.subject.gokfull	Neuropathologie	de
dc.identifier.ppn	590188283	de

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