| dc.contributor.advisor | Jahn, Reinhard Prof. Dr. | |
| dc.contributor.author | Binotti, Beyenech | |
| dc.date.accessioned | 2015-02-26T10:56:38Z | |
| dc.date.available | 2015-02-26T10:56:38Z | |
| dc.date.issued | 2015-02-26 | |
| dc.identifier.uri | http://hdl.handle.net/11858/00-1735-0000-0022-5DD6-6 | |
| dc.identifier.uri | http://dx.doi.org/10.53846/goediss-4952 | |
| dc.language.iso | eng | de |
| dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/3.0/ | |
| dc.subject.ddc | 570 | de |
| dc.title | Rab26 mediates selective targeting of synaptic vesicles to the autophagy pathway | de |
| dc.type | doctoralThesis | de |
| dc.contributor.referee | Rehling, Peter Prof. Dr. | |
| dc.date.examination | 2014-03-17 | |
| dc.description.abstracteng | In recent years it has been shown that macroautophagy regulates the turnover of postsynaptic receptors and modulates presynaptic neurotransmission. However it is still unclear whether the presynaptic protein turnover is regulated by the same pathway. It was previously shown in our laboratory that the small GTPase Rab26 is highly enriched in the synaptic vesicle fraction (Nathan Pavlos, unpublished data). The real implication of its presence on the synaptic vesicle membranes though has not been investigated so far. The aim of this project was to characterize the functional role of Rab26 in neurons. We wanted to find out in which pathway Rab26 is implicated and if it contributes in regulating the synaptic vesicle (SV) cycle. I employed well established biochemical and cell biology approaches such as immunoprecipitation, GST pulldown, immunoisolation as well as immunocytochemistry and electron microscopy to address these questions. The systems in which I applied these techniques were cultured hippocampal neurons, HeLa ss6 and HEK 293T cell lines. During this study it was possible to obtain several findings. I could demonstrate that Rab26 is a neuronal small GTPase Rab protein which is associated with a subset of synaptic vesicles. It has the ability to oligomerize, to cluster vesicles and it interacts with one of the essential core components of the autophagosome machinery, Atg16L1. Furthermore it is selectively targeting recycled synaptic vesicles. This led us to conclude that Rab26 might be an important key regulator of synaptic vesicle quality control. Furthermore the identification of the interaction between Rab26 and Atg16L1 made it possible to connect recycled synaptic vesicles with the autophagy pathway. In addition we could offer an alternative mode of synaptic vesicle endocytosis that bypasses the Rab5-dependent pathway and converges with the late endosome/autolysosome pathway. All these aspects listed here will be discussed further in detail in the following paragraphs. | de |
| dc.contributor.coReferee | Simons, Mikael Prof. Dr. | |
| dc.subject.eng | Synaptic vesicle | de |
| dc.subject.eng | Rab protein | de |
| dc.subject.eng | Autophagy | de |
| dc.identifier.urn | urn:nbn:de:gbv:7-11858/00-1735-0000-0022-5DD6-6-4 | |
| dc.affiliation.institute | Göttinger Graduiertenschule für Neurowissenschaften, Biophysik und molekulare Biowissenschaften (GGNB) | de |
| dc.subject.gokfull | Biologie (PPN619462639) | de |
| dc.identifier.ppn | 819037869 | |