Munc18 function in large dense-core vesicle exocytosis

Gulyas-Kovacs, Attila

dc.contributor.advisor	Neher, Erwin Prof. Dr.	de
dc.contributor.author	Gulyas-Kovacs, Attila	de
dc.date.accessioned	2012-04-16T14:56:39Z	de
dc.date.available	2013-01-30T23:51:02Z	de
dc.date.issued	2005-03-23	de
dc.identifier.uri	http://hdl.handle.net/11858/00-1735-0000-0006-ABB0-E	de
dc.identifier.uri	http://dx.doi.org/10.53846/goediss-622
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	Munc18 function in large dense-core vesicle exocytosis	de
dc.type	doctoralThesis	de
dc.title.translated	Munc18 function in large dense-core vesicle exocytosis	de
dc.contributor.referee	Neher, Erwin Prof. Dr.	de
dc.date.examination	2005-01-26	de
dc.subject.dnb	570 Biowissenschaften, Biologie	de
dc.description.abstracteng	Neurotransmitter and hormon release is based on Ca2+ dependent exocytosis. The sequential steps of exocytosis are executed by proteins and protein complexes. Formation of the SNARE complex is essential in later steps of exocytosis. The Sec1/Munc18 proteins are also essential in exocytosis and other membrane trafficking processes but their molecular and cellular function is less clear than that of the SNARE proteins.In our work we studied the role of Munc18 in large dense-core vesicle exocytosis in adrenal chromaffin cells. We combined complementary techniques (electrophysiology, electronmicroscopy) to assay docking, priming and Ca2+ triggered fusion of the vesicles. First, we further confirmed the view that Munc18-1 is a positive regulator of large dense-core vesicle exocytosis. Second, we were interested the downstream molecular targets of Munc18-1 therefore we studied the physiological role of Munc18-1/syntaxin1 interaction. We showed that this interaction is highly important in functional vesicle docking but further experiments are needed to decide whether it is the only major factor or there are other essential downstream targets for Munc18-1. Third, we studied different Munc18 isoforms and our results imply that Munc18 may act not only at the docking but also at the priming step of large dense-core exocytosis. Although some publications argue for the regulatory role of Munc18 in single vesicle fusion kinetics, we found no sign for the direct involvement of Munc18 in Ca2+ triggered fusion. Fourth, we also focused on the upstream regulation of Munc18-1. We obtained opposing data to the hypothesis that Munc18-1 is an important element of the phorbol ester induced potentiation of catecholamine release in the diacylglycerol (DAG) route. The DAG pathway remains an important but poorly understood regulator of transmitter/hormon release, which probably has multiple branches targeting multiple molecules and exocytic steps. Taken together, our findings provided inspiring hints about many aspects of Munc18 function in Ca2+ dependent exocytosis. Perhaps the most important aspect is to match the consecutive steps of exocytosis with the molecular happenings along the Munc18/syntaxin complex SNARE complex axis. Our complementary assays combined with the gene knockout and rescue technique could promote adrenal chromaffin cells to become the first system where this match between cellular function and molecular structure is clarified.	de
dc.contributor.coReferee	Heinrich, Ralf Prof. Dr.	de
dc.subject.topic	Mathematics and Computer Science	de
dc.subject.eng	exocytosis	de
dc.subject.eng	Munc18	de
dc.subject.eng	chromaffin cells	de
dc.subject.eng	exocytosis	de
dc.subject.eng	Munc18	de
dc.subject.eng	chromaffin cells	de
dc.identifier.urn	urn:nbn:de:gbv:7-webdoc-65-8	de
dc.identifier.purl	webdoc-65	de
dc.affiliation.institute	Biologische Fakultät inkl. Psychologie	de
dc.subject.gokfull	WC 000 Biophysik; WH 000 Zytologie	de
dc.subject.gokfull	Histologie	de
dc.subject.gokfull	Zellbiologie	de
dc.subject.gokfull	Zellkultur	de
dc.subject.gokfull	Zytologie WC Biophysik; WH Cytologie	de
dc.subject.gokfull	Histologie	de
dc.subject.gokfull	Zellbiologie	de
dc.subject.gokfull	Zellkultur	de
dc.subject.gokfull	Zytologie	de
dc.identifier.ppn	484712837	de

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Fakultät für Biologie und Psychologie (inkl. GAUSS) [1621]

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