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Cited by 15Cellular transport and secretionAutophagy in Disease and TherapyExtracellular vesicles in disease

Selective cargo and membrane recognition by SNX17 regulates its interaction with Retriever

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Martín-González, Aurora, Méndez-Guzmán, Iván, Zabala-Zearreta, Maialen, Quintanilla, Andrea, García-López, Arturo, Martínez-Lombardía, Eva, Albesa-Jové, David, Acosta, Juan Carlos +1 more·2025·EMBO Reports
DOI 10.1038/s44319-024-00340-1PMC PMC11772769
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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.

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  • SNX17 is an endosomal adaptor that functions in concert with the Retriever complex to promote LDLR recycling and interacts with LDLR NPxY motif.

    “SNX17 is an endosomal adaptor that functions in concert with the Retriever complex to promote LDLR recycling and interacts with LDLR NPxY motif 26 .”

    From Dietary cholesterol activates a Ral-dependent pathway driving LDLR turnover (2026) · cites this paper as [26]

    The Introduction says SNX17 engages NPxY-containing cargo and helps recruit Retriever to endosomal membranes; it also reports LDLR as a Retriever-recycled protein. But the Results test binding to LRP1 (low-density lipoprotein receptor-related protein 1), not LDLR, and our copy does not establish that SNX17 interacts with the LDLR NPxY motif or specifically promotes LDLR recycling. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

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Cited by

Sorted by citations

Authors
Martín-González, A., Méndez-Guzmán, I., Zabala-Zearreta, M., Quintanilla, A., García-López, A., Martínez-Lombardía, E., Albesa-Jové, D., Acosta, J. C., & Lucas, M.
Affiliations
  • Universidad de Cantabria (ES)
  • University of the Basque Country (ES)
  • Ikerbasque (ES)
Corresponding author
Lucas, María
ORCID
Venue
EMBO Reports
Publisher
Springer Science and Business Media LLC
Published
2024-12-09
Volume
26
Issue
2
Pages
470-493
ISSN
  • 1469-221X (ISSN-L)
  • 1469-3178
DOI
10.1038/s44319-024-00340-1
PMC
PMC11772769
OpenAlex
W4405173761
Cited by
15
References
2
Citations by year
2026: 3 · 2025: 12
FWCI
3.18
Type
journal article
Language
en
Open access
Licence
Locations
  • EMBO Reports (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DIGITAL.CSIC (Spanish National Research Council (CSIC)) (acceptedVersion, other-oa)
  • UCrea (University of Cantabria) (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Ministerio de Ciencia e Innovación (RTI2018-097801-B-I00, PID2021-122611NB-100, TED2021-129278B-I00, PID2021-127816NB-I00, PID2020-117860GB-I00, RYC-2016-20342, PRE2019-088459)
  • Eusko Jaurlaritza (IT1745-22, PRE_2023_1_0100)
  • Banco Santander
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
  • Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
Keywords
SNX17, cargo recognition, membrane recognition, phosphatidylinositol 3-phosphate, protein-membrane interactions
MeSH terms
Binding Sites, Cell Membrane, Humans, Models, Molecular, Protein Binding, Endosomes, Phosphatidylinositol Phosphates, Protein Transport, Vesicular Transport Proteins, Sorting Nexins

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