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A SNX3-dependent retromer pathway mediates retrograde transport of the Wnt sorting receptor Wntless and is required for Wnt secretion

Harterink, Martin, Port, Fillip, Lorenowicz, Magdalena J., McGough, Ian J., Silhankova, Marie, Betist, Marco C., van Weering, Jan R. T., van Heesbeen, Roy G. H. P., Middelkoop, Teije C., Basler, Konrad, Cullen, Peter J., Korswagen, Hendrik C.·2011·Nature Cell Biology
DOI 10.1038/ncb2281PMC PMC4052212
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Crossref · 10.1038/ncb2281

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  • SNX3 directly binds to a subset of cargo containing the sequence motif [+/-]-x-∅-x-[L/M], with many of these cargoes trafficked through the retrograde endosome-to-TGN pathway.

    “SNX3 directly binds to a subset of cargo containing the poorly defined sequence motif [+/-]-x-∅-x-[L/M] (∅ -bulky aromatic residue) with many of these cargoes trafficked through the retrograde endosome-to-TGN pathway [25,30,66,67].”

    From Global identification of neuronal and astrocytic integral membrane proteins that require Retromer for their endosomal recycling (2026) · cites this paper as [25]

    The Results section reports that SNX3 directly binds the VPS26–VPS29–VPS35 retromer complex and participates in Wntless trafficking. The Abstract says the cargo-selective retromer subcomplex—not SNX3—binds a sorting motif in cargo proteins. The copy does not identify the claimed [+/-]-x-∅-x-[L/M] motif or establish direct SNX3 binding to cargo bearing it. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • The SNX3-Retromer assembly is essential for the sequence-dependent retrieval and recycling of cargoes.

    “An additional cargo adaptor complex essential for the sequence-dependent retrieval and recycling of cargoes is the sorting nexin-3 (SNX3)-Retromer assembly [25,30,66,67].”

    From Global identification of neuronal and astrocytic integral membrane proteins that require Retromer for their endosomal recycling (2026) · cites this paper as [25]

    The Discussion (page not specified) identifies an SNX3–retromer pathway that retrieves and recycles Wntless (Wls), supporting the assembly’s role in cargo recycling. It does not establish that SNX3–retromer retrieval is sequence-dependent for cargoes generally; the Discussion says the authors did not observe an interaction between SNX3 and Wls. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

  • Endosomal retrieval and recycling is orchestrated through a specialised endosomal nanodomain, the retrieval sub-domain.

    “and is orchestrated through a specialised endosomal nanodomain, the retrieval sub-domain”

    From Mapping of endosomal proximity proteomes reveals Retromer as a hub for RAB GTPase regulation (2025) · cites this paper as [8]

    The Results and Discussion describe SNX3-dependent retrieval and recycling of Wntless through a vesicular endosomal pathway distinct from the SNX-BAR tubular pathway. They do not identify a specialised endosomal nanodomain called the “retrieval sub-domain” or establish that endosomal retrieval and recycling generally is orchestrated through one. The indexed passages provide no page numbers. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

  • Retromer associates with accessory proteins and cargo adaptors including sorting nexins, the WASH complex, RAB GTPase regulators including TBC1D5 and ANKRD27/VARP, and RME8.

    “To function, Retromer associates with accessory proteins and cargo adaptors including sorting nexins (SNXs) [24][25][26][27][28][29][30][31][32][33][34], the WASH complex [35][36][37][38][39], RAB GTPase regulators including TBC1D5 and ANKRD27/VARP [40][41][42][43][44][45][46], and RME8 [47].”

    From Global identification of neuronal and astrocytic integral membrane proteins that require Retromer for their endosomal recycling (2026) · cites this paper as [25]

  • Endosomal cargo retrieval and recycling are orchestrated by several multi-protein assemblies including SNX27-Retromer and SNX3-Retromer, SNX17-Retriever and associated Commander super-assembly, the WASH complex and its regulatory MUST complex, and the SNX-BAR proteins and ESCPE-1.

    “Orchestrating endosomal cargo retrieval and recycling are several multi-protein assemblies that include sorting nexin-27 (SNX27)-Retromer and SNX3-Retromer8–16, SNX17-Retriever and associated Commander super-assembly17–22, the branched F-actin polymerising WASH complex and its regulatory MAGE-L2/USP7/TRIM27 (MUST) complex23–25, and the SNX-BAR proteins and endosomal sorting complex required for ex”

    From Mapping of endosomal proximity proteomes reveals Retromer as a hub for RAB GTPase regulation (2025) · cites this paper as [8]

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Citations

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Research works printed but not linked: 54

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Metadata

Authors
Harterink, M., Port, F., Lorenowicz, M. J., McGough, I. J., Silhankova, M., Betist, M. C., van Weering, J. R. T., van Heesbeen, R. G. H. P., Middelkoop, T. C., Basler, K., Cullen, P. J., & Korswagen, H. C.
Venue
Nature Cell Biology
Publisher
Springer Science and Business Media LLC
Published
2011-07-03
Volume
13
Issue
8
Pages
914-923
ISSN
  • 1465-7392
  • 1476-4679
DOI
10.1038/ncb2281
PMC
PMC4052212
Cited by
327
References
2
Language
en
Licence
www.springer.com/tdm (tdm)

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