The DOI matches its Crossref record.
Retromer has a selective function in cargo sorting via endosome transport carriers
Abstract
Retromer is a peripheral membrane protein complex that coordinates multiple vesicular trafficking events within the endolysosomal system. Here, we demonstrate that retromer is required for the maintenance of normal lysosomal morphology and function. The knockout of retromer subunit Vps35 causes an ultrastructural alteration in lysosomal structure and aberrant lysosome function, leading to impaired autophagy. At the whole-cell level, knockout of retromer Vps35 subunit reduces lysosomal proteolytic capacity as a consequence of the improper processing of lysosomal hydrolases, which is dependent on the trafficking of the cation-independent mannose 6-phosphate receptor (CI-M6PR). Incorporation of CI-M6PR into endosome transport carriers via a retromer-dependent process is restricted to those tethered by GCC88 but not golgin-97 or golgin-245. Finally, we show that this retromer-dependent retrograde cargo trafficking pathway requires SNX3, but not other retromer-associated cargo binding proteins, such as SNX27 or SNX-BAR proteins. Therefore, retromer does contribute to the retrograde trafficking of CI-M6PR required for maturation of lysosomal hydrolases and lysosomal function.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Loss of retromer leads to impaired mTORC1 activity, induction of autophagy, and the appearance of swollen and evenly dispersed lysosomes.
“This leads to impaired mTORC1 activity and the induction of autophagy, and the appearance of swollen and evenly dispersed lysosomes (Jimenez-Orgaz et al., 2018; Cui et al., 2019; Curnock et al., 2019; Kvainickas et al., 2019).”
From Acute inactivation of retromer and ESCPE-1 leads to time-resolved defects in endosomal cargo sorting (2020) · cites this paper as Cui et al., 2019
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
No references could be resolved yet.
Research works printed but not linked: 71
- Arighi, 2004, Role of the mammalian retromer in sorting of the cation-independent mannose 6-phosphate receptor, J. Cell Biol., 165, 123, 10.1083/jcb.200312055 · DOI · Paper page
- Arlt, 2015, Retromer and the dynamin Vps1 cooperate in the retrieval of transmembrane proteins from vacuoles, J. Cell Sci., 128, 645, 10.1242/jcs.132720 · DOI
- Bolte, 2006, A guided tour into subcellular colocalization analysis in light microscopy, J. Microsc., 224, 213, 10.1111/j.1365-2818.2006.01706.x · DOI
- Breusegem, 2014, Genome-wide RNAi screen reveals a role for multipass membrane proteins in endosome-to-golgi retrieval, Cell Reports., 9, 1931, 10.1016/j.celrep.2014.10.053 · DOI
- Bright, 2016, Endolysosomes Are the Principal Intracellular Sites of Acid Hydrolase Activity, Curr. Biol., 26, 2233, 10.1016/j.cub.2016.06.046 · DOI
- Bröcker, 2010, Multisubunit tethering complexes and their role in membrane fusion, Curr. Biol., 20, R943, 10.1016/j.cub.2010.09.015 · DOI
- Bugarcic, 2011, Vps26A and Vps26B subunits define distinct retromer complexes, Traffic., 12, 1759, 10.1111/j.1600-0854.2011.01284.x · DOI
- Bulankina, 2009, TIP47 functions in the biogenesis of lipid droplets, J. Cell Biol., 185, 641, 10.1083/jcb.200812042 · DOI
- Carlton, 2004, Sorting nexin-1 mediates tubular endosome-to-TGN transport through coincidence sensing of high- curvature membranes and 3-phosphoinositides, Curr. Biol., 14, 1791, 10.1016/j.cub.2004.09.077 · DOI · Paper page
- Clairfeuille, 2016, A molecular code for endosomal recycling of phosphorylated cargos by the SNX27-retromer complex, Nat. Struct. Mol. Biol., 23, 921, 10.1038/nsmb.3290 · DOI · Paper page
- Collins, 2008, Structure of Vps26B and mapping of its interaction with the retromer protein complex, Traffic., 9, 366, 10.1111/j.1600-0854.2007.00688.x · DOI
- Díaz, 1998, TIP47: a cargo selection device for mannose 6-phosphate receptor trafficking, Cell., 93, 433, 10.1016/S0092-8674(00)81171-X · DOI
- Elwell, 2017, Chlamydia interfere with an interaction between the mannose-6-phosphate receptor and sorting nexins to counteract host restriction, eLife., 6, e22709, 10.7554/eLife.22709 · DOI
- Follett, 2014, The Vps35 D620N mutation linked to Parkinson’s disease disrupts the cargo sorting function of retromer, Traffic., 15, 230, 10.1111/tra.12136 · DOI
- Ghosh, 2003, Mannose 6-phosphate receptors: new twists in the tale, Nat. Rev. Mol. Cell Biol., 4, 202, 10.1038/nrm1050 · DOI
- Gillingham, 2016, Finding the Golgi: Golgin Coiled-Coil Proteins Show the Way, Trends Cell Biol., 26, 399, 10.1016/j.tcb.2016.02.005 · DOI
- Goberdhan, 2016, Amino Acid Sensing by mTORC1: Intracellular Transporters Mark the Spot, Cell Metab., 23, 580, 10.1016/j.cmet.2016.03.013 · DOI
- Gokool, 2007, Identification of a conserved motif required for Vps35p/Vps26p interaction and assembly of the retromer complex, Biochem. J., 408, 287, 10.1042/BJ20070555 · DOI
- Gomez, 2009, A FAM21-containing WASH complex regulates retromer-dependent sorting, Dev. Cell., 17, 699, 10.1016/j.devcel.2009.09.009 · DOI · Paper page
- Hara, 2008, The DHR1 domain of DOCK180 binds to SNX5 and regulates cation-independent mannose 6-phosphate receptor transport, Mol. Biol. Cell., 19, 3823, 10.1091/mbc.e08-03-0314 · DOI
- Harbour, 2010, The cargo-selective retromer complex is a recruiting hub for protein complexes that regulate endosomal tubule dynamics, J. Cell Sci., 123, 3703, 10.1242/jcs.071472 · DOI · Paper page
- Harbour, 2012, Recruitment of the endosomal WASH complex is mediated by the extended ‘tail’ of Fam21 binding to the retromer protein Vps35, Biochem. J., 442, 209, 10.1042/BJ20111761 · DOI · Paper page
- Harrison, 2014, A mechanism for retromer endosomal coat complex assembly with cargo, Proc. Natl. Acad. Sci. USA., 111, 267, 10.1073/pnas.1316482111 · DOI
- Harterink, 2011, A SNX3-dependent retromer pathway mediates retrograde transport of the Wnt sorting receptor Wntless and is required for Wnt secretion, Nat. Cell Biol., 13, 914, 10.1038/ncb2281 · DOI · Paper page
- Hierro, 2007, Functional architecture of the retromer cargo-recognition complex, Nature., 449, 1063, 10.1038/nature06216 · DOI · Paper page
- Hirst, 2018, Role of the AP-5 adaptor protein complex in late endosome-to-Golgi retrieval, PLoS Biol., 16, e2004411, 10.1371/journal.pbio.2004411 · DOI
- Hong, 2009, The retromer component SNX6 interacts with dynactin p150(Glued) and mediates endosome-to-TGN transport, Cell Res., 19, 1334, 10.1038/cr.2009.130 · DOI
- Jia, 2012, Multiple repeat elements within the FAM21 tail link the WASH actin regulatory complex to the retromer, Mol. Biol. Cell., 23, 2352, 10.1091/mbc.e11-12-1059 · DOI · Paper page
- Kerr, 2005, A novel mammalian retromer component, Vps26B, Traffic., 6, 991, 10.1111/j.1600-0854.2005.00328.x · DOI · Paper page
- Kerr, 2006, Visualisation of macropinosome maturation by the recruitment of sorting nexins, J. Cell Sci., 119, 3967, 10.1242/jcs.03167 · DOI
- Kerr, 2017, Laser-mediated rupture of chlamydial inclusions triggers pathogen egress and host cell necrosis, Nat. Commun., 8, 14729, 10.1038/ncomms14729 · DOI
- Kingston, 2011, Inhibition of retromer activity by herpesvirus saimiri tip leads to CD4 downregulation and efficient T cell transformation, J. Virol., 85, 10627, 10.1128/JVI.00757-11 · DOI
- Kolodny, 1976, Human leukocyte acid hydrolases: characterization of eleven lysosomal enzymes and study of reaction conditions for their automated analysis, Clin. Chim. Acta., 70, 247, 10.1016/0009-8981(76)90426-5 · DOI
- Kvainickas, 2017, Cargo-selective SNX-BAR proteins mediate retromer trimer independent retrograde transport, J. Cell Biol., 216, 3677, 10.1083/jcb.201702137 · DOI · Paper page
- Leaback, 1961, Studies on glucosaminidase. 4. The fluorimetric assay of N-acetyl-beta-glucosaminidase, Biochem. J., 78, 151, 10.1042/bj0780151 · DOI
- Lenoir, 2018, Phosphorylation of conserved phosphoinositide binding pocket regulates sorting nexin membrane targeting, Nat. Commun., 9, 993, 10.1038/s41467-018-03370-1 · DOI · Paper page
- Lieu, 2010, Identification of different itineraries and retromer components for endosome-to-Golgi transport of TGN38 and Shiga toxin, Eur. J. Cell Biol., 89, 379, 10.1016/j.ejcb.2009.10.021 · DOI
- Lieu, 2007, The golgin GCC88 is required for efficient retrograde transport of cargo from the early endosomes to the trans-Golgi network, Mol. Biol. Cell., 18, 4979, 10.1091/mbc.e07-06-0622 · DOI
- Lucas, 2016, Structural mechanism for cargo recognition by the retromer complex, Cell., 167, 1623, 10.1016/j.cell.2016.10.056 · DOI · Paper page
- Markmann, 2015, Lrp1/LDL Receptor Play Critical Roles in Mannose 6-Phosphate-Independent Lysosomal Enzyme Targeting, Traffic., 16, 743, 10.1111/tra.12284 · DOI
- Maruzs, 2015, Retromer Ensures the Degradation of Autophagic Cargo by Maintaining Lysosome Function in Drosophila, Traffic., 16, 1088, 10.1111/tra.12309 · DOI
- McGough, 2014, Retromer binding to FAM21 and the WASH complex is perturbed by the Parkinson disease-linked VPS35(D620N) mutation, Curr. Biol., 24, 1670, 10.1016/j.cub.2014.06.024 · DOI · Paper page
- McKenzie, 2012, Retromer guides STxB and CD8-M6PR from early to recycling endosomes, EHD1 guides STxB from recycling endosome to Golgi, Traffic., 13, 1140, 10.1111/j.1600-0854.2012.01374.x · DOI
- Meyer, 2000, mu1A-adaptin-deficient mice: lethality, loss of AP-1 binding and rerouting of mannose 6-phosphate receptors, EMBO J., 19, 2193, 10.1093/emboj/19.10.2193 · DOI · Paper page
- Miura, 2014, VPS35 dysfunction impairs lysosomal degradation of α-synuclein and exacerbates neurotoxicity in a Drosophila model of Parkinson’s disease, Neurobiol. Dis., 71, 1, 10.1016/j.nbd.2014.07.014 · DOI
- Mizushima, 2010, Methods in mammalian autophagy research, Cell., 140, 313, 10.1016/j.cell.2010.01.028 · DOI · Paper page
- Munro, 2011, The golgin coiled-coil proteins of the Golgi apparatus, Cold Spring Harb. Perspect. Biol., 3, a005256, 10.1101/cshperspect.a005256 · DOI
- Osborne, 2015, Monitoring receptor trafficking following retromer and WASH deregulation, Methods Cell Biol., 130, 199, 10.1016/bs.mcb.2015.03.018 · DOI
- Parton, 1989, Meeting of the apical and basolateral endocytic pathways of the Madin-Darby canine kidney cell in late endosomes, J. Cell Biol., 109, 3259, 10.1083/jcb.109.6.3259 · DOI
- Priya, 2017, Essential and selective role of SNX12 in transport of endocytic and retrograde cargo, J. Cell Sci., 130, 2707, 10.1242/jcs.201905 · DOI
- Rojas, 2008, Regulation of retromer recruitment to endosomes by sequential action of Rab5 and Rab7, J. Cell Biol., 183, 513, 10.1083/jcb.200804048 · DOI · Paper page
- Roy, 2017, Autophagy-dependent shuttling of TBC1D5 controls plasma membrane translocation of GLUT1 and glucose uptake, Mol. Cell., 67, 84, 10.1016/j.molcel.2017.05.020 · DOI
- Saftig, 2009, Lysosome biogenesis and lysosomal membrane proteins: trafficking meets function, Nat. Rev. Mol. Cell Biol., 10, 623, 10.1038/nrm2745 · DOI · Paper page
- Saint-Pol, 2004, Clathrin adaptor epsinR is required for retrograde sorting on early endosomal membranes, Dev. Cell., 6, 525, 10.1016/S1534-5807(04)00100-5 · DOI
- Scott, 2006, A PACS-1, GGA3 and CK2 complex regulates CI-MPR trafficking, EMBO J., 25, 4423, 10.1038/sj.emboj.7601336 · DOI
- Seaman, 2004, Cargo-selective endosomal sorting for retrieval to the Golgi requires retromer, J. Cell Biol., 165, 111, 10.1083/jcb.200312034 · DOI · Paper page
- Seaman, 2007, Identification of a novel conserved sorting motif required for retromer-mediated endosome-to-TGN retrieval, J. Cell Sci., 120, 2378, 10.1242/jcs.009654 · DOI
- Seaman, 2012, The retromer complex—endosomal protein recycling and beyond, J. Cell Sci., 125, 4693, 10.1242/jcs.103440 · DOI · Paper page
- Seaman, 2018, Retromer and the cation-independent mannose 6-phosphate receptor-Time for a trial separation?, Traffic., 19, 150, 10.1111/tra.12542 · DOI
- Seaman, 2009, Membrane recruitment of the cargo-selective retromer subcomplex is catalysed by the small GTPase Rab7 and inhibited by the Rab-GAP TBC1D5, J. Cell Sci., 122, 2371, 10.1242/jcs.048686 · DOI · Paper page
- Settembre, 2013, Signals from the lysosome: a control centre for cellular clearance and energy metabolism, Nat. Rev. Mol. Cell Biol., 14, 283, 10.1038/nrm3565 · DOI
- Shin, 2017, TBC1D23 is a bridging factor for endosomal vesicle capture by golgins at the trans-Golgi, Nat. Cell Biol., 19, 1424, 10.1038/ncb3627 · DOI
- Simonetti, 2017, Sequence-dependent cargo recognition by SNX-BARs mediates retromer-independent transport of CI-MPR, J. Cell Biol., 216, 3695, 10.1083/jcb.201703015 · DOI · Paper page
- Tabuchi, 2010, Retromer-mediated direct sorting is required for proper endosomal recycling of the mammalian iron transporter DMT1, J. Cell Sci., 123, 756, 10.1242/jcs.060574 · DOI
- Tammineni, 2017, Impaired axonal retrograde trafficking of the retromer complex augments lysosomal deficits in Alzheimer’s disease neurons, Hum. Mol. Genet., 26, 4352, 10.1093/hmg/ddx321 · DOI
- Vardarajan, 2012, Identification of Alzheimer disease-associated variants in genes that regulate retromer function, Neurobiol. Aging., 33, e2215, 10.1016/j.neurobiolaging.2012.04.020 · DOI · Paper page
- Wang, 2014, The retromer complex is required for rhodopsin recycling and its loss leads to photoreceptor degeneration, PLoS Biol., 12, e1001847, 10.1371/journal.pbio.1001847 · DOI
- Wassmer, 2007, A loss-of-function screen reveals SNX5 and SNX6 as potential components of the mammalian retromer, J. Cell Sci., 120, 45, 10.1242/jcs.03302 · DOI · Paper page
- Wong, 2014, Membrane trafficking. The specificity of vesicle traffic to the Golgi is encoded in the golgin coiled-coil proteins, Science., 346, 1256898, 10.1126/science.1256898 · DOI
- Wong, 2017, The golgin coiled-coil proteins capture different types of transport carriers via distinct N-terminal motifs, BMC Biol., 15, 3, 10.1186/s12915-016-0345-3 · DOI
- Yang, 2016, Functional characterization of retromer in GLUT4 storage vesicle formation and adipocyte differentiation, FASEB J., 30, 1037, 10.1096/fj.15-274704 · DOI
Cited by
Sorted by citations
The Retromer Complex: From Genesis to Revelations
Seaman, M. N. J. (2021) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2020.12.009 · Cited by 104
Pharmacological modulation of autophagy for Alzheimer's disease therapy: Opportunities and obstacles
Deng, Z., Dong, Y., Zhou, X., Lu, J.-H., & Yue, Z. (2022) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2021.12.009 · Cited by 58
Receptor Recycling by Retromer
Carosi, J. M., Denton, D., Kumar, S., & Sargeant, T. J. (2023) · Molecular and Cellular Biology · doi:10.1080/10985549.2023.2222053 · Cited by 36
Self-citationThe Alzheimer's Disease Gene SORL1 Regulates Lysosome Function in Human Microglia
Mishra, S., Morshed, N., Sidhu, S. B., Kinoshita, C., Stevens, B., Jayadev, S., & Young, J. E. (2025) · Glia · doi:10.1002/glia.70009 · Cited by 31
Acute inactivation of retromer and ESCPE-1 leads to time-resolved defects in endosomal cargo sorting
Evans, A. J., Daly, J. L., Anuar, A. N. K., Simonetti, B., & Cullen, P. J. (2020) · Journal of Cell Science · doi:10.1242/jcs.246033 · Cited by 25
Retromer dysfunction at the nexus of tauopathies
Carosi, J. M., Denton, D., Kumar, S., & Sargeant, T. J. (2021) · Cell Death & Differentiation · doi:10.1038/s41418-020-00727-2 · Cited by 16
Self-citation
Metadata
- Authors
- Cui, Y., Carosi, J. M., Yang, Z., Ariotti, N., Kerr, M. C., Parton, R. G., Sargeant, T. J., & Teasdale, R. D.
- Affiliations
- School of Biomedical Sciences, Faculty of Medicine, The University of Queensland, Brisbane, Queensland, Australia 1
- Hopwood Centre for Neurobiology, Nutrition and Metabolism Theme, South Australian Health and Medical Research Institute, Adelaide, South Australia, Australia 2
- Institute for Molecular Biosciences and Centre for Microscopy and Microanalysis, The University of Queensland, Brisbane, Queensland, Australia 4
- Venue
- Journal of Cell Biology
- Publisher
- Rockefeller University Press
- Published
- 2018-12-17
- Volume
- 218
- Issue
- 2
- Pages
- 615-631
- ISSN
- 0021-9525
- 1540-8140
- PMC
- PMC6363445
- Cited by
- 152
- References
- 0
- Language
- en
- Funders
- Australian Research Council (DP160101573)
- National Health and Medical Research Council (APP1037320, APP1058565, APP569542, APP1045092, APP1041929)
- China Scholarship Council
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review