[{"tmp":{"short":"CC BY (4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png"},"acknowledgement":"We thank A.-M. Lawrence-Dörner and B. Berkenfeld for technical assistance and the members of the Kümmel Lab for constructive feedback. We are grateful to C. Ungermann and L. Langemeyer for insightful discussions and to F. Barr for providing plasmids encoding Fuzzy, Inturned, Rab23, and Rsg1. The template clone Flag-ciBAR1 was a gift from K.-I. Takemaru (Addgene, plasmid #200440). We thank the Bloomington Drosophila Stock center (BDSC) and DSHB for providing fly stocks and antibodies. This work was supported by the German Research Foundation (DFG) through the grants SFB1557-P10 (D.K.), SFB1557-P11 (A.M.), and SFB1577-P6, PA517/12-2, PA517/14-1, PA517/15-1, and PA517/16-1 (A.P.). Cryo-EM data were collected at the infrastructure of the University of Osnabrück, funded by the DFG (project number 455249646). J.-H.S. was supported by the Friedrich-Ebert Foundation. M.L. acknowledges funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (grant agreement number 101045340).","isi":1,"intvolume":"        11","file_date_updated":"2025-09-15T07:23:12Z","user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","publication":"Science Advances","volume":11,"date_published":"2025-08-29T00:00:00Z","oa_version":"Published Version","publication_status":"published","publisher":"AAAS","language":[{"iso":"eng"}],"OA_type":"gold","OA_place":"publisher","has_accepted_license":"1","publication_identifier":{"eissn":["2375-2548"]},"citation":{"ieee":"S. Wilmes <i>et al.</i>, “Mechanistic adaptation of the metazoan RabGEFs Mon1-Ccz1 and Fuzzy-Inturned,” <i>Science Advances</i>, vol. 11, no. 35. AAAS, p. eadx2893, 2025.","chicago":"Wilmes, Stephan, Jesse Tönjes, Maik Drechsler, Anita Ruf, Jan Hannes Schäfer, Anna Lürick, Dovile Januliene, et al. “Mechanistic Adaptation of the Metazoan RabGEFs Mon1-Ccz1 and Fuzzy-Inturned.” <i>Science Advances</i>. AAAS, 2025. <a href=\"https://doi.org/10.1126/sciadv.adx2893\">https://doi.org/10.1126/sciadv.adx2893</a>.","short":"S. Wilmes, J. Tönjes, M. Drechsler, A. Ruf, J.H. Schäfer, A. Lürick, D. Januliene, S. Apelt, D. Di Iorio, S.V. Wegner, M. Loose, A. Moeller, A. Paululat, D. Kümmel, Science Advances 11 (2025) eadx2893.","ista":"Wilmes S, Tönjes J, Drechsler M, Ruf A, Schäfer JH, Lürick A, Januliene D, Apelt S, Di Iorio D, Wegner SV, Loose M, Moeller A, Paululat A, Kümmel D. 2025. Mechanistic adaptation of the metazoan RabGEFs Mon1-Ccz1 and Fuzzy-Inturned. Science Advances. 11(35), eadx2893.","ama":"Wilmes S, Tönjes J, Drechsler M, et al. Mechanistic adaptation of the metazoan RabGEFs Mon1-Ccz1 and Fuzzy-Inturned. <i>Science Advances</i>. 2025;11(35):eadx2893. doi:<a href=\"https://doi.org/10.1126/sciadv.adx2893\">10.1126/sciadv.adx2893</a>","mla":"Wilmes, Stephan, et al. “Mechanistic Adaptation of the Metazoan RabGEFs Mon1-Ccz1 and Fuzzy-Inturned.” <i>Science Advances</i>, vol. 11, no. 35, AAAS, 2025, p. eadx2893, doi:<a href=\"https://doi.org/10.1126/sciadv.adx2893\">10.1126/sciadv.adx2893</a>.","apa":"Wilmes, S., Tönjes, J., Drechsler, M., Ruf, A., Schäfer, J. H., Lürick, A., … Kümmel, D. (2025). Mechanistic adaptation of the metazoan RabGEFs Mon1-Ccz1 and Fuzzy-Inturned. <i>Science Advances</i>. AAAS. <a href=\"https://doi.org/10.1126/sciadv.adx2893\">https://doi.org/10.1126/sciadv.adx2893</a>"},"department":[{"_id":"MaLo"}],"pmid":1,"external_id":{"pmid":["40864718"],"isi":["001559806100033"]},"_id":"20351","date_updated":"2025-09-30T14:40:27Z","article_processing_charge":"Yes","issue":"35","type":"journal_article","file":[{"access_level":"open_access","creator":"dernst","date_updated":"2025-09-15T07:23:12Z","relation":"main_file","file_id":"20355","checksum":"a3de801f3c6c1deadd7099d965db799a","file_size":3434827,"success":1,"file_name":"2025_ScienceAdvance_Wilmes.pdf","content_type":"application/pdf","date_created":"2025-09-15T07:23:12Z"}],"oa":1,"date_created":"2025-09-14T22:01:32Z","abstract":[{"text":"Rab GTPases organize intracellular trafficking and provide identity to organelles. Their spatiotemporal activation by guanine nucleotide exchange factors (GEFs) is tightly controlled to ensure fidelity. Our structural and functional comparison of the tri-longin domain RabGEFs Mon1-Ccz1 and Fuzzy-Inturned reveals the molecular basis for their target specificity. Both complexes rely on a conserved sequence motif of their substrate GTPases for the catalytic mechanism, while secondary interactions allow discrimination between targets. We also find that dimeric Mon1-Ccz1 from fungi and the metazoan homologs with the additional third subunit RMC1/Bulli bind membranes through electrostatic interactions via distinct interfaces. Protein-lipid interaction studies and functional characterization in flies reveal an essential function of RMC1/Bulli as mediator of GEF complex membrane recruitment. In the case of Fuzzy-Inturned, reconstitution experiments demonstrate that the BAR (Bin-Amphiphysin-Rvs) domain protein CiBAR1 can support membrane recruitment of the GEF. Collectively, our study demonstrates the molecular basis for the adaptation of TLD-RabGEFs to different cellular functions.","lang":"eng"}],"status":"public","quality_controlled":"1","article_type":"original","day":"29","DOAJ_listed":"1","scopus_import":"1","page":"eadx2893","project":[{"_id":"bd6ae2ca-d553-11ed-ba76-a4aa239da5ee","grant_number":"101045340","name":"Synthetic and structural biology of Rab GTPase networks"}],"author":[{"first_name":"Stephan","last_name":"Wilmes","full_name":"Wilmes, Stephan"},{"full_name":"Tönjes, Jesse","last_name":"Tönjes","first_name":"Jesse"},{"full_name":"Drechsler, Maik","last_name":"Drechsler","first_name":"Maik"},{"first_name":"Anita","last_name":"Ruf","full_name":"Ruf, Anita"},{"first_name":"Jan Hannes","last_name":"Schäfer","full_name":"Schäfer, Jan Hannes"},{"full_name":"Lürick, Anna","last_name":"Lürick","first_name":"Anna"},{"full_name":"Januliene, Dovile","first_name":"Dovile","last_name":"Januliene"},{"full_name":"Apelt, Steven","last_name":"Apelt","first_name":"Steven"},{"full_name":"Di Iorio, Daniele","first_name":"Daniele","last_name":"Di Iorio"},{"full_name":"Wegner, Seraphine V.","first_name":"Seraphine V.","last_name":"Wegner"},{"orcid":"0000-0001-7309-9724","last_name":"Loose","first_name":"Martin","full_name":"Loose, Martin","id":"462D4284-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Moeller","first_name":"Arne","full_name":"Moeller, Arne"},{"last_name":"Paululat","first_name":"Achim","full_name":"Paululat, Achim"},{"first_name":"Daniel","last_name":"Kümmel","full_name":"Kümmel, Daniel"}],"doi":"10.1126/sciadv.adx2893","year":"2025","title":"Mechanistic adaptation of the metazoan RabGEFs Mon1-Ccz1 and Fuzzy-Inturned","month":"08","ddc":["570"],"PlanS_conform":"1"},{"article_type":"original","doi":"10.1016/j.devcel.2023.06.001","year":"2023","project":[{"name":"In vitro reconstitution of bacterial cell division","_id":"fc38323b-9c52-11eb-aca3-ff8afb4a011d","grant_number":"P34607"},{"_id":"bd6ae2ca-d553-11ed-ba76-a4aa239da5ee","grant_number":"101045340","name":"Synthetic and structural biology of Rab GTPase networks"}],"author":[{"full_name":"Leonard, Thomas A.","first_name":"Thomas A.","last_name":"Leonard"},{"last_name":"Loose","first_name":"Martin","orcid":"0000-0001-7309-9724","full_name":"Loose, Martin","id":"462D4284-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Sascha","last_name":"Martens","full_name":"Martens, Sascha"}],"page":"1315-1332","scopus_import":"1","day":"07","month":"08","title":"The membrane surface as a platform that organizes cellular and biochemical processes","ddc":["570"],"oa":1,"file":[{"relation":"main_file","access_level":"open_access","creator":"dernst","date_updated":"2023-08-14T07:57:55Z","checksum":"d8c5dc97cd40c26da2ec98ae723ab368","file_size":3184217,"file_id":"14049","file_name":"2023_DevelopmentalCell_Leonard.pdf","date_created":"2023-08-14T07:57:55Z","content_type":"application/pdf","success":1}],"type":"journal_article","abstract":[{"text":"Membranes are essential for life. They act as semi-permeable boundaries that define cells and organelles. In addition, their surfaces actively participate in biochemical reaction networks, where they confine proteins, align reaction partners, and directly control enzymatic activities. Membrane-localized reactions shape cellular membranes, define the identity of organelles, compartmentalize biochemical processes, and can even be the source of signaling gradients that originate at the plasma membrane and reach into the cytoplasm and nucleus. The membrane surface is, therefore, an essential platform upon which myriad cellular processes are scaffolded. In this review, we summarize our current understanding of the biophysics and biochemistry of membrane-localized reactions with particular focus on insights derived from reconstituted and cellular systems. We discuss how the interplay of cellular factors results in their self-organization, condensation, assembly, and activity, and the emergent properties derived from them.","lang":"eng"}],"date_created":"2023-08-13T22:01:12Z","quality_controlled":"1","status":"public","corr_author":"1","has_accepted_license":"1","language":[{"iso":"eng"}],"external_id":{"isi":["001059110400001"],"pmid":["37419118"]},"department":[{"_id":"MaLo"}],"pmid":1,"publication_identifier":{"eissn":["1878-1551"],"issn":["1534-5807"]},"citation":{"apa":"Leonard, T. A., Loose, M., &#38; Martens, S. (2023). The membrane surface as a platform that organizes cellular and biochemical processes. <i>Developmental Cell</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.devcel.2023.06.001\">https://doi.org/10.1016/j.devcel.2023.06.001</a>","short":"T.A. Leonard, M. Loose, S. Martens, Developmental Cell 58 (2023) 1315–1332.","ista":"Leonard TA, Loose M, Martens S. 2023. The membrane surface as a platform that organizes cellular and biochemical processes. Developmental Cell. 58(15), 1315–1332.","ama":"Leonard TA, Loose M, Martens S. The membrane surface as a platform that organizes cellular and biochemical processes. <i>Developmental Cell</i>. 2023;58(15):1315-1332. doi:<a href=\"https://doi.org/10.1016/j.devcel.2023.06.001\">10.1016/j.devcel.2023.06.001</a>","mla":"Leonard, Thomas A., et al. “The Membrane Surface as a Platform That Organizes Cellular and Biochemical Processes.” <i>Developmental Cell</i>, vol. 58, no. 15, Elsevier, 2023, pp. 1315–32, doi:<a href=\"https://doi.org/10.1016/j.devcel.2023.06.001\">10.1016/j.devcel.2023.06.001</a>.","ieee":"T. A. Leonard, M. Loose, and S. Martens, “The membrane surface as a platform that organizes cellular and biochemical processes,” <i>Developmental Cell</i>, vol. 58, no. 15. Elsevier, pp. 1315–1332, 2023.","chicago":"Leonard, Thomas A., Martin Loose, and Sascha Martens. “The Membrane Surface as a Platform That Organizes Cellular and Biochemical Processes.” <i>Developmental Cell</i>. Elsevier, 2023. <a href=\"https://doi.org/10.1016/j.devcel.2023.06.001\">https://doi.org/10.1016/j.devcel.2023.06.001</a>."},"article_processing_charge":"Yes (via OA deal)","date_updated":"2024-10-22T11:40:18Z","_id":"14039","issue":"15","isi":1,"acknowledgement":"We acknowledge funding from the Austrian Science Fund (FWF F79, P32814-B, and P35061-B to S.M.; P34607-B to M.L.; and P30584-B and P33066-B to T.A.L.) and the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (grant agreement no. 101045340 to M.L.). We are grateful for comments on the manuscript by Justyna Sawa-Makarska, Verena Baumann, Marko Kojic, Philipp Radler, Ronja Reinhardt, and Sumire Antonioli.","tmp":{"short":"CC BY (4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png"},"publication":"Developmental Cell","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","intvolume":"        58","file_date_updated":"2023-08-14T07:57:55Z","oa_version":"Published Version","date_published":"2023-08-07T00:00:00Z","volume":58,"publisher":"Elsevier","publication_status":"published"}]