@article{10902/35257,
year = {2024},
url = {https://hdl.handle.net/10902/35257},
abstract = {The Retriever complex recycles a wide range of transmembrane proteins from endosomes to the plasma membrane. The cargo adapter protein SNX17 has been implicated in recruiting the Retriever complex to endosomal membranes, yet the details of this interaction have remained elusive. Through biophysical and structural model-guided mutagenesis studies with recombinant proteins and liposomes, we have gained a deeper understanding of this process. Here, we demonstrate a direct interaction between SNX17 and Retriever, specifically between the C-terminal region of SNX17 and the interface of the Retriever subunits VPS35L and VPS26C. This interaction is enhanced upon the binding of SNX17 to its cargo in solution, due to the disruption of an intramolecular autoinhibitory interaction between the C-terminal region of SNX17 and the cargo binding pocket. In addition, SNX17 binding to membranes containing phosphatidylinositol-3-phosphate also promotes Retriever recruitment in a cargo-independent manner. Therefore, this work provides evidence of the dual activation mechanisms by which SNX17 modulates Retriever recruitment to the proximity of cargo and membranes, offering significant insights into the regulatory mechanisms of protein recycling at endosomes.},
organization = {We are extremely grateful to Victor Campa for his assistance in confocal fluorescence microscopy and the staff of beamline B21 of Diamond Light Source for SAXS measurements. This work was supported by grants from the Agencia Estatal de Investigación of Ministerio de Ciencia e Innovación (MCIN/AEI/ 10.13039/501100011033) RTI2018-097801-B-I00, PID2021-122611NB-100, and TED2021-129278B-I00 to ML, PID2020-117860GB-I00 to JCA and grant PID2021-127816NB-I00 to DA-J. Moreover, funding by MCIN/AEI/10.13039/ 501100011033 and by “ESF Investing in your future” to ML (RYC-2016-20342) and AM-G (PRE2019-088459) is acknowledged. DA-J was also funded by Fundación Biofísica Bizkaia, the Basque Excellence Research Centre (BERC) program, and IT1745-22 of the Basque Government. MZ-Z acknowledges support from the Basque Government predoctoral program (PRE_2023_1_0100). IM-G received support from Banco Santander through a Ph.D. contract.},
publisher = {Wiley},
publisher = {EMBO Reports, 2025, 26, 470-493},
title = {Selective cargo and membrane recognition by SNX17 regulates its interaction with Retriever},
author = {Martín González, Aurora and Méndez Guzmán, Iván and Zabala-Zearreta, Maialen and Quintanilla Cavia, Andrea and García López, Arturo and Martínez Lombardía, Eva and Albesa Jové, David and Acosta Cobacho, Juan Carlos and Lucas Gay, María},
}