SNX3-retromer requires an evolutionary conserved MON2:DOPEY2:ATP9A complex to mediate Wntless sorting and Wnt secretion

McGough, Ian J.; Groot, Reinoud E. A. de; Jellett, Adam P.; Betist, Marco C.; Varandas, Katherine C.; Danson, Chris M.; Heesom, Kate J; Korswagen, Hendrik C.; Cullen, Peter J.

doi:10.1038/s41467-018-06114-3

Cited by 64 publications

(65 citation statements)

References 79 publications

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“…At a superficial level, the mammalian heterodimers of SNX1 (or SNX2) with SNX5 (or SNX6) are localised to endosomal structures that generally co‐localise with the core Retromer trimer by confocal fluorescence microscopy, and an interaction between mammalian Retromer and the SNX‐BAR proteins has been observed using yeast two hybrid assays and co‐immunoprecipitation . In contrast, super‐resolved stimulated emission depletion (STED) microscopy suggested that Vps35 and SNX1 occupy distinct domains on the endosome, and the interaction of Retromer with the SNX‐BAR proteins appears to be very weak compared to other known ligands such as SNX3 and SNX27 . Several recent studies have brought this link between Retromer and SNX‐BAR proteins in higher eukaryotes into sharper focus .…”

Section: The Retromer and Snx‐bar Controversymentioning

confidence: 99%

“…Together with Rab7, SNX3 is important for the stable recruitment and activity of Retromer on endosomal membranes . SNX3‐Retromer is involved in the retrograde transport of cargo receptors including the Wnt sorting receptor Wntless, transferrin receptor, the divalent metal ion transporter Dmt1‐II, and CI‐MPR, in carriers that are morphologically and functionally distinct from the SNX‐BAR proteins in higher eukaryotes . It has also been suggested that the SNX3 homologue SNX12 can perform a similar role .…”

Section: Snx Proteins As Retromer Cargo Adaptorsmentioning

confidence: 99%

“…SNX3‐Retromer is involved in the retrograde transport of cargo receptors including the Wnt sorting receptor Wntless, transferrin receptor, the divalent metal ion transporter Dmt1‐II, and CI‐MPR, in carriers that are morphologically and functionally distinct from the SNX‐BAR proteins in higher eukaryotes . It has also been suggested that the SNX3 homologue SNX12 can perform a similar role . The crystal structure of a complex of SNX3, Vps26 and Vps35 bound to a short peptide motif from the Dmt1‐II protein reveals the mechanism for these cargo interactions (Figure A).…”

Section: Snx Proteins As Retromer Cargo Adaptorsmentioning

confidence: 99%

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Towards a molecular understanding of endosomal trafficking by Retromer and Retriever

Chen

Healy

Collins

2019

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www.traf c.dkCover legend: Retromer is essen al in all eukaryotes for the traffi cking of transmembrane proteins within membrane tubules. Cryoelectron microscopy was used to show how retromer assembles with membrane-bound sor ng nexin proteins to form these membrane tubules. The picture shows a modelled segment of the retromersor ng nexin coat. See Chen et al. (Traffi c 2019; 20(7):465-478). Read the full ar cle on Aim and ScopeTraffic encourages and facilitates the publication of papers covering the cell biology of intracellular transport in health and disease. Areas of interest include protein, nucleic acid and lipid traffic, molecular motors, intracellular pathogens, intracellular proteolysis, nuclear import and export, cytokinesis and the cell cycle, protein translocation, antigen processing and presentation, organelle biogenesis, metabolism, cell polarity and organization, and organelle movement.All aspects of the structural, molecular biology, biochemistry, genetics, morphology, intracellular signaling and relationship to hereditary or infectious diseases will be covered. Manuscripts must provide a clear conceptual or mechanistic advance. The editors will reject papers that require major changes, including addition of significant experimental data or other significant revision.

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Section: The Retromer and Snx‐bar Controversymentioning

confidence: 99%

Section: Snx Proteins As Retromer Cargo Adaptorsmentioning

confidence: 99%

Section: Snx Proteins As Retromer Cargo Adaptorsmentioning

confidence: 99%

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Towards a molecular understanding of endosomal trafficking by Retromer and Retriever

Chen

Healy

Collins

2019

Traffic

152

144

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“…This included AP-1 adaptors (AP1G1, AP1S2, AP1AR, AP1M1 and AP1S1) and accessory proteins (CLINT1, SYNRG, PI4K2B and Rab9), but not their associated clathrin coat (15,17,24,25). We also found proteins involved in retromer-dependent transport (SNX3, SNX4, VPS35, VPS26, VPS29), along with SNX-BAR proteins potentially involved in retromer-independent transport (SNX1, SNX2, SNX5 and SNX6) (26)(27)(28). Many peripheral membrane proteins are localised to multiple compartments in the cell, making them difficult to classify by spatial proteomics (Fig.…”

Section: Adaptor Proteins and Accessory Factors Of Vesicles Specific mentioning

confidence: 83%

Determining the content of vesicles captured by golgin tethers using LOPIT-DC

Shin

Crook²,

Borgeaud

et al. 2019

Preprint

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The internal organisation of the cell depends on tethers at destination organelles to selectively capture incoming transport vesicles to facilitate SNARE-mediated fusion. The golgin long coiledcoil proteins function as tethers that contributes to this specificity at the Golgi (1). Golgin-97, golgin-245 and GCC88 golgins of the trans-Golgi capture vesicles derived from endosomes, which serve to recycle the critical Golgi machinery required to deliver lysosomal hydrolases and to maintain exocytosis. Retrograde trafficking from endosomes to the trans-Golgi network (TGN) is a complex process that involves the sorting of transmembrane cargo proteins into distinct transport vesicles by adaptors from multiple pathways. The content of these distinct vesicles, which golgin they target and the factors that mediate this targeting are not well understood. The major challenges that have limited advances in these areas is the transient nature of vesicle tethering, and the redundancies in their mechanisms that confound experimental dissection. To gain better insight into these problems, we performed organelle proteomics using the Localisation of Organelle Proteins by Isotope Tagging after Differential ultraCentrifugation (LOPIT-DC) method on a system in which an ectopic golgin causes vesicles to accumulate in a tethered state (2). By incorporating Bayesian statistical modelling into our analysis (3), we determined that over 45 transmembrane proteins and 51 peripheral membrane proteins of the endosomal network are on vesicles captured by golgin-97, including known cargo and components of the clathrin/AP-1, retromer-dependent and -independent transport pathways. We also determined a distinct class of vesicles shared by golgin-97, golgin-245 and GCC88 that is enriched in TMEM87A, a multi-pass transmembrane protein of unknown function that has previously been implicated in endosome-to-Golgi retrograde transport (4). Finally, we categorically demonstrate that the vesicles that these golgins capture are retrograde transport vesicles based on the lack of enrichment of lysosomal hydrolases in our LOPIT-DC data, and from correlative light electron tomography images of spherical vesicles captured by golgin-97. Together, our study demonstrates the power of combining LOPIT-DC with Bayesian statistical analysis in interrogating the dynamic spatial movement of proteins in transport vesicles.

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“…When Wnt is present in the cytoplasm, (Fig. 1B), it will be lipidated by a special palmitoyl transferase-porcupine [34], further modified by Wntless in the Golgi and finally secreted by exocytosis [35,36]. Frizzled (FZD) receptors, the principal receptors for Wnts, consist of seven-transmembrane proteins and cysteine-rich domain (CRD) in the N-terminal [37,38].…”

Section: Canonical Wnt Pathway Activation Mechanismmentioning

confidence: 99%