{"publication_identifier":{"issn":["2663-337X"]},"page":"215","doi":"10.15479/AT:ISTA:8341","has_accepted_license":"1","author":[{"orcid":"0000-0003-1365-5631","id":"2A58201A-F248-11E8-B48F-1D18A9856A87","full_name":"Bezeljak, Urban","first_name":"Urban","last_name":"Bezeljak"}],"language":[{"iso":"eng"}],"_id":"8341","citation":{"ama":"Bezeljak U. In vitro reconstitution of a Rab activation switch. 2020. doi:<a href=\"https://doi.org/10.15479/AT:ISTA:8341\">10.15479/AT:ISTA:8341</a>","ista":"Bezeljak U. 2020. In vitro reconstitution of a Rab activation switch. Institute of Science and Technology Austria.","apa":"Bezeljak, U. (2020). <i>In vitro reconstitution of a Rab activation switch</i>. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/AT:ISTA:8341\">https://doi.org/10.15479/AT:ISTA:8341</a>","chicago":"Bezeljak, Urban. “In Vitro Reconstitution of a Rab Activation Switch.” Institute of Science and Technology Austria, 2020. <a href=\"https://doi.org/10.15479/AT:ISTA:8341\">https://doi.org/10.15479/AT:ISTA:8341</a>.","short":"U. Bezeljak, In Vitro Reconstitution of a Rab Activation Switch, Institute of Science and Technology Austria, 2020.","mla":"Bezeljak, Urban. <i>In Vitro Reconstitution of a Rab Activation Switch</i>. Institute of Science and Technology Austria, 2020, doi:<a href=\"https://doi.org/10.15479/AT:ISTA:8341\">10.15479/AT:ISTA:8341</a>.","ieee":"U. Bezeljak, “In vitro reconstitution of a Rab activation switch,” Institute of Science and Technology Austria, 2020."},"year":"2020","acknowledged_ssus":[{"_id":"Bio"},{"_id":"LifeSc"},{"_id":"NanoFab"}],"ddc":["570"],"acknowledgement":"My thanks goes to the Loose lab members, BioImaging, Life Science and Nanofabrication Facilities and the wonderful international community at IST for sharing this experience with me.","file_date_updated":"2021-09-16T12:49:12Z","article_processing_charge":"No","month":"09","supervisor":[{"orcid":"0000-0001-7309-9724","id":"462D4284-F248-11E8-B48F-1D18A9856A87","full_name":"Loose, Martin","last_name":"Loose","first_name":"Martin"}],"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by-nc-sa/4.0/legalcode","short":"CC BY-NC-SA (4.0)","image":"/images/cc_by_nc_sa.png","name":"Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)"},"date_updated":"2023-09-07T13:17:06Z","file":[{"checksum":"70871b335a595252a66c6bbf0824fb02","relation":"source_file","access_level":"closed","creator":"dernst","file_name":"2020_Urban_Bezeljak_Thesis_TeX.zip","content_type":"application/x-zip-compressed","date_updated":"2021-09-16T12:49:12Z","file_size":65246782,"date_created":"2020-09-08T09:00:29Z","file_id":"8342"},{"access_level":"open_access","creator":"dernst","file_name":"2020_Urban_Bezeljak_Thesis.pdf","content_type":"application/pdf","checksum":"59a62275088b00b7241e6ff4136434c7","relation":"main_file","file_size":31259058,"date_created":"2020-09-08T09:00:27Z","file_id":"8343","date_updated":"2021-09-16T12:49:12Z"}],"type":"dissertation","license":"https://creativecommons.org/licenses/by-nc-sa/4.0/","day":"08","degree_awarded":"PhD","department":[{"_id":"MaLo"}],"abstract":[{"lang":"eng","text":"One of the most striking hallmarks of the eukaryotic cell is the presence of intracellular vesicles and organelles. Each of these membrane-enclosed compartments has a distinct composition of lipids and proteins, which is essential for accurate membrane traffic and homeostasis. Interestingly, their biochemical identities are achieved with the help\r\nof small GTPases of the Rab family, which cycle between GDP- and GTP-bound forms on the selected membrane surface. While this activity switch is well understood for an individual protein, how Rab GTPases collectively transition between states to generate decisive signal propagation in space and time is unclear. In my PhD thesis, I present\r\nin vitro reconstitution experiments with theoretical modeling to systematically study a minimal Rab5 activation network from bottom-up. We find that positive feedback based on known molecular interactions gives rise to bistable GTPase activity switching on system’s scale. Furthermore, we determine that collective transition near the critical\r\npoint is intrinsically stochastic and provide evidence that the inactive Rab5 abundance on the membrane can shape the network response. Finally, we demonstrate that collective switching can spread on the lipid bilayer as a traveling activation wave, representing a possible emergent activity pattern in endosomal maturation. Together, our\r\nfindings reveal new insights into the self-organization properties of signaling networks away from chemical equilibrium. Our work highlights the importance of systematic characterization of biochemical systems in well-defined physiological conditions. This way, we were able to answer long-standing open questions in the field and close the gap between regulatory processes on a molecular scale and emergent responses on system’s level."}],"date_published":"2020-09-08T00:00:00Z","publication_status":"published","publisher":"Institute of Science and Technology Austria","oa":1,"oa_version":"Published Version","date_created":"2020-09-08T08:53:53Z","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","alternative_title":["ISTA Thesis"],"title":"In vitro reconstitution of a Rab activation switch","related_material":{"record":[{"status":"public","relation":"part_of_dissertation","id":"7580"}]},"status":"public"}