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.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.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.doi http://dx.doi.org/10.15252/embr.202256134
- dc.identifier.issn 1469-221X
- dc.identifier.uri http://hdl.handle.net/10230/56279
- dc.language.iso eng
- dc.publisher EMBO Press
- dc.relation.ispartof EMBO Rep. 2023 May 4;24(5):e56134
- 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 © 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.accessRights info:eu-repo/semantics/openAccess
- dc.rights.uri http://creativecommons.org/licenses/by-nc-nd/4.0/
- dc.subject.keyword Atg9
- dc.subject.keyword Cvt pathway
- dc.subject.keyword Drs2
- dc.subject.keyword TRAPPIII
- dc.subject.keyword Vesicle transport
- 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.type.version info:eu-repo/semantics/publishedVersion