Polarized Traffic of LRP1 Involves AP1B and SNX17 Operating on Y-dependent Sorting Motifs in Different Pathways
Open accessAbstract
Low-density lipoprotein receptor–related protein 1 (LRP1) is an endocytic recycling receptor with two cytoplasmic tyrosine-based basolateral sorting signals. Here we show that during biosynthetic trafficking LRP1 uses AP1B adaptor complex to move from a post-TGN recycling endosome (RE) to the basolateral membrane. Then it recycles basolaterally from the basolateral sorting endosome (BSE) involving recognition by sorting nexin 17 (SNX17). In the biosynthetic pathway, Y 29 but not N 26 from a proximal NPXY directs LRP1 basolateral sorting from the TGN. A N 26 A mutant revealed that this NPXY motif recognized by SNX17 is required for the receptor's exit from BSE. An endocytic Y 63 ATL 66 motif also functions in basolateral recycling, in concert with an additional endocytic motif (LL 86,87), by preventing LRP1 entry into the transcytotic apical pathway. All this sorting information operates similarly in hippocampal neurons to mediate LRP1 somatodendritic distribution regardless of the absence of AP1B in neurons. LRP1 basolateral distribution results then from spatially and temporally segregation steps mediated by recognition of distinct tyrosine-based motifs. We also demonstrate a novel function of SNX17 in basolateral/somatodendritic recycling from a different compartment than AP1B endosomes.
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
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?
Both the PX domain and the FERM domain are required for recruitment of SNX17 to the endosomal membrane.
“Both the PX domain and the FERM domain, through binding to the cargo, are required for the recruitment of SNX17 to the endosomal membrane [35], [36].”
From Sorting nexin 17 regulates ApoER2 recycling and reelin signaling (2014) · cites this paper as [36]
The Results (p. 489) report that wild-type LRP1 promotes SNX17 recruitment to EEA1-positive early endosomes more than an N26A cargo mutant. The paper does not establish that both the PX and FERM domains are required for that recruitment. (LLM, conf=0.88)
Experimental — accuracy not yet measuredSNX17 participates in the basolateral and somatodendritic recycling of LRP1 in polarized epithelial and neuronal cells respectively.
“Recently, we proposed that SNX17 also participates in the basolateral and somatodendritic recycling of LRP1 in polarized epithelial and neuronal cells respectively [36].”
From Sorting nexin 17 regulates ApoER2 recycling and reelin signaling (2014) · cites this paper as [36]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Rat hippocampal neurons in dispersed cell culture.
Banker, G. A., & Cowan, W. M. (1977) · Brain Research · doi:10.1016/0006-8993(77)90594-7 · Cited by 1,110 · see citing works
Flagged first, then by citations
Research works printed but not linked: 1
- [180]180. Simmen, T., Honing, S., Icking, A., Tikkanen, R., and Hunziker, W. (2002). AP-4 binds basolateral signals and participates in basolateral sorting in epi- thelial MDCK cells. Nat. Cell Biol. 4, 154–159. Soza, A., Norambuena, A., Cancino, J., De La Fuente, E., Henklein, P., and Gonzalez, A. (2004). Sorting competition with membrane-permeable peptides in intact epithelial cells revealed discrimination of transmembrane proteins not only at the trans-golgi network but also at pre-golgi stages. J. Biol. Chem. 279, 17376–17383. Stockinger, W., Sailler, B., Strasser, V., Recheis, B., Fasching, D., Kahr, L., Schneider, W. J., and Nimpf, J. (2002). The PX-domain protein SNX17 interacts with members of the LDL receptor family and modulates endocytosis of the LDL receptor. EMBO J. 21, 4259–4267. Sugimoto, H. et al. (2002). Differential recognition of tyrosine-based basolat- eral signals by AP-1B subunit mu1B in polarized epithelial cells. Mol. Biol. Cell 13, 2374–2382. van Kerkhof, P., Lee, J., McCormick, L., Tetrault, E., Lu, W., Schoenfish, M., Oorschot, V., Strous, G. J., Klumperman, J., and Bu, G. (2005). Sorting nexin 17 facilitates LRP recycling in the early endosome. EMBO J. 24, 2851–2861. Wilson, J. M., de Hoop, M., Zorzi, N., Toh, B. H., Dotti, C. G., and Parton, R. G. (2000). EEA1, a tethering protein of the early sorting endosome, shows a polarized distribution in hippocampal neurons, epithelial cells, and fibro- blasts [In Process Citation]. Mol. Biol. Cell 11, 2657–2671. Winckler, B., and Mellman, I. (1999). Neuronal polarity: controlling the sort- ing and diffusion of membrane components. Neuron 23, 637–640. Worby, C. A., and Dixon, J. E. (2002). Sorting out the cellular functions of sorting nexins. Nat. Rev. Mol. Cell Biol. 3, 919–931. Yap, C. C., Murate, M., Kishigami, S., Muto, Y., Kishida, H., Hashikawa, T., and Yano, R. (2003). Adaptor protein complex-4 (AP-4) is expressed in the central nervous system neurons and interacts with glutamate receptor delta2. Mol. Cell Neurosci. 24, 283–295. Yeaman, C., Grindstaff, K. K., and Nelson, W. J. (1999). New perspectives on mechanisms involved in generating epithelial cell polarity. Physiol. Rev. 79, 73–98. Zhuo, M., Holtzman, D. M., Li, Y., Osaka, H., DeMaro, J., Jacquin, M., and Bu, G. (2000). Role of tissue plasminogen activator receptor LRP in hippocampal long-term potentiation. J. Neurosci. 20, 542–549. LRP1 Sorting in Polarized Cells Vol. 20, January 1, 2009 497
Cited by
Sorted by citations
Functional Roles of the Interaction of APP and Lipoprotein Receptors
Pohlkamp, T., Wasser, C. R., & Herz, J. (2017) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2017.00054 · Cited by 92 · see citing works
Sorting nexin 17 regulates ApoER2 recycling and reelin signaling
Sotelo, P., Farfán, P., Benitez, M. L., Bu, G., & Marzolo, M.-P. (2014) · PLoS ONE · doi:10.1371/journal.pone.0093672 · Cited by 47 · see citing works
Self-citation
- Authors
- Donoso, M., Cancino, J., Lee, J., van Kerkhof, P., Retamal, C., Bu, G., Gonzalez, A., Cáceres, A., & Marzolo, M.-P.
- Affiliations
- Pontificia Universidad Católica de Chile (CL)
- Washington University in St. Louis (US)
- Department of Cell Biology and Institute of Biomembranes, University Medical Center, Utrech 3584 CX, The Netherlands;
- *Centro de Regulación Celular y Patología (CRCP), Departamento de Biología Celular y Molecular, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile (PUC) and the Millenium Institute for Fundamental and Applied Biology (MIFAB), Santiago, Chile;
- Consejo Nacional de Investigaciones Científicas y Técnicas (AR)
- Venue
- Molecular Biology of the Cell
- Published
- 2009-01
- Volume
- 20
- Issue
- 1
- Pages
- 481-497
- ISSN
- 1059-1524 (ISSN-L)
- 1939-4586
- PMC
- PMC2613102
- OpenAlex
- W2122999827
- Cited by
- 69
- References
- 1
- Citations by year
- 2026: 3 · 2024: 7 · 2023: 2 · 2022: 5 · 2021: 2 · 2020: 4 · 2019: 2 · 2018: 5 · 2017: 5 · 2016: 3 · 2015: 5 · 2014: 2 · 2013: 9 · 2012: 7
- FWCI
- 1.09
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Molecular Biology of the Cell (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Digital Commons@Becker (Washington University School of Medicine) (submittedVersion)
- Rare & Special e-Zone (The Hong Kong University of Science and Technology) (submittedVersion)
- Americanae (AECID Library) (submittedVersion, other-oa)
- Americanae (AECID Library) (submittedVersion, cc-by-nc-nd)
- LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (submittedVersion, other-oa)
- LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (submittedVersion, cc-by-nc-nd)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion)
- Funders
- American Health Assistance Foundation
- American Heart Association
- Institut National de la Santé et de la Recherche Médicale
- Consejo Nacional de Investigaciones Científicas y Técnicas
- Centre National de la Recherche Scientifique (UMR8104)
- National Institutes of Health (AG027924)
- Genentech
- Agencia Nacional de Promoción Científica y Tecnológica (CONICET)
- National Institute on Aging (P01AG030128, R01AG027924, R01AG035355)
- Fogarty International Center (R03TW006456)
- Fondo de Financiamiento de Centros de Investigación en Áreas Prioritarias
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- LRP1, basolateral sorting, SNX17, sorting nexins, NPXY motif, recycling endosomes, endocytic recycling, transcytosis, hippocampal neurons, receptor trafficking
- MeSH terms
- Animals, Cell Line, Cell Membrane, Epithelial Cells, Golgi Apparatus, Humans, Molecular Sequence Data, Mutation, Neurons, Endosomes, Cell Polarity, Protein Transport, Protein Sorting Signals, trans-Golgi Network, Low Density Lipoprotein Receptor-Related Protein-1, Vesicular Transport Proteins, Adaptor Protein Complex 1, Adaptor Protein Complex beta Subunits
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
