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

Pazos, Irene; Puig-Tintó, Marta; Betancur, Laura; Cordero, Jorge; Jiménez-Menéndez, Nereida; Abella, Marc; Hernández, Altair C.; Duran, Ana G.; Adachi-Fernández, Emi; Belmonte Mateos, Carla, 1992-; Sabido-Bozo, Susana; Tosi, Sebastien; Nezu, Akiko; Oliva Miguel, Baldomero; Colombelli, Julien; Graham, Todd R.; Yoshimori, Tamotsu; Muñiz, Manuel; Hamasaki, Maho; Gallego, Oriol

doi:http://dx.doi.org/10.15252/embr.202256134

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

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

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.