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The P4-ATPase Drs2 interacts with and stabilizes the multisubunit tethering complex TRAPPIII in yeast

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dc.contributor.author Pazos, Irene
dc.contributor.author Puig-Tintó, Marta
dc.contributor.author Betancur, Laura
dc.contributor.author Cordero, Jorge
dc.contributor.author Jiménez-Menéndez, Nereida
dc.contributor.author Abella, Marc
dc.contributor.author Hernández, Altair C.
dc.contributor.author Duran, Ana G.
dc.contributor.author Adachi-Fernández, Emi
dc.contributor.author Belmonte Mateos, Carla, 1992-
dc.contributor.author Sabido-Bozo, Susana
dc.contributor.author Tosi, Sebastien
dc.contributor.author Nezu, Akiko
dc.contributor.author Oliva Miguel, Baldomero
dc.contributor.author Colombelli, Julien
dc.contributor.author Graham, Todd R.
dc.contributor.author Yoshimori, Tamotsu
dc.contributor.author Muñiz, Manuel
dc.contributor.author Hamasaki, Maho
dc.contributor.author Gallego, Oriol
dc.date.accessioned 2023-03-20T07:37:38Z
dc.date.available 2023-03-20T07:37:38Z
dc.date.issued 2023
dc.identifier.citation Pazos I, Puig-Tintó M, Betancur L, Cordero J, Jiménez-Menéndez N, Abella M, Hernández AC, Duran AG, Adachi-Fernández E, Belmonte-Mateos C, Sabido-Bozo S, Tosi S, Nezu A, Oliva B, Colombelli J, Graham TR, Yoshimori T, Muñiz M, Hamasaki M, Gallego O. The P4-ATPase Drs2 interacts with and stabilizes the multisubunit tethering complex TRAPPIII in yeast. EMBO Rep. 2023 May 4;24(5):e56134. DOI: 10.15252/embr.202256134
dc.identifier.issn 1469-221X
dc.identifier.uri http://hdl.handle.net/10230/56279
dc.description.abstract Multisubunit Tethering Complexes (MTCs) are a set of conserved protein complexes that tether vesicles at the acceptor membrane. Interactions with other components of the trafficking machinery regulate MTCs through mechanisms that are partially understood. Here, we systematically investigate the interactome that regulates MTCs. We report that P4-ATPases, a family of lipid flippases, interact with MTCs that participate in the anterograde and retrograde transport at the Golgi, such as TRAPPIII. We use the P4-ATPase Drs2 as a paradigm to investigate the mechanism and biological relevance of this interplay during transport of Atg9 vesicles. Binding of Trs85, the sole-specific subunit of TRAPPIII, to the N-terminal tail of Drs2 stabilizes TRAPPIII on membranes loaded with Atg9 and is required for Atg9 delivery during selective autophagy, a role that is independent of P4-ATPase canonical functions. This mechanism requires a conserved I(S/R)TTK motif that also mediates the interaction of the P4-ATPases Dnf1 and Dnf2 with MTCs, suggesting a broader role of P4-ATPases in MTC regulation.
dc.description.sponsorship OG was funded by research grants from the Spanish funding agency (PGC2018-095745-B-I00, EUR2019-103815 and PID2021-127773NB-I00/FEDER UE and supported by the “Unidad de Excelencia María de Maeztu” (ref: MDM-2014-0370) funded by the MCIN/AEI/10.13039/501100011033) and a Research Grant from HFSP (ref: RGP0017/2020). The proteomics analyses were performed in the CRG/UPF Proteomics Unit which is part of the of Proteored, PRB3 and is supported by grant PT17/0019, of the PE I + D + i 2013-2016, funded by ISCIII and ERDF. We thank Josep Vilardell, Bernat Crosas, Amy Curwin, Vivek Malhotra, Michael Knop, Marko Kaksonen, Kenji Maeda, Manuel García-Muñiz and Charles Boone for providing devices, reagents, strains and plasmids. We thank the Advanced Digital Microscopy Core Facility (ADMCF), the Biostatistics/Bioinformatics and the Mass Spectrometry and Proteomics facilities of the IRB Barcelona for live-cell imaging, technical support and also sharing devices with us. We thank Simona Barankova, Radovan Dojcilovic and Daniel Castaño-Díez for fruitful discussions. We thank Raúl Méndez and Ignasi Fita for their support and mentoring during these years. IP was supported by FPI awarded by the Spanish Ministry of Economy and Competitiveness (MINECO) (ref: BES-2013-063945) and EMBO Short-Term Fellowship 7076.
dc.format.mimetype application/pdf
dc.language.iso eng
dc.publisher EMBO Press
dc.relation.ispartof EMBO Rep. 2023 May 4;24(5):e56134
dc.rights © 2023 The Authors. Published under the terms of the CC BY NC ND 4.0 license. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
dc.rights.uri http://creativecommons.org/licenses/by-nc-nd/4.0/
dc.title The P4-ATPase Drs2 interacts with and stabilizes the multisubunit tethering complex TRAPPIII in yeast
dc.type info:eu-repo/semantics/article
dc.identifier.doi http://dx.doi.org/10.15252/embr.202256134
dc.subject.keyword Atg9
dc.subject.keyword Cvt pathway
dc.subject.keyword Drs2
dc.subject.keyword TRAPPIII
dc.subject.keyword Vesicle transport
dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/PGC2018-095745-B-I00
dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/EUR2019-103815
dc.relation.projectID info:eu-repo/grantAgreement/ES/3PE/PID2021-127773NB-I00
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.type.version info:eu-repo/semantics/publishedVersion

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