The DOI matches its Crossref record; 8 of the 8 references it cites were found in a registry or an index.
Flotillin-Dependent Clustering of the Amyloid Precursor Protein Regulates Its Endocytosis and Amyloidogenic Processing in Neurons
Open accessAbstract
The flotillins/reggie proteins are associated with noncaveolar membrane microdomains and have been implicated in the regulation of a clathrin- and caveolin-independent endocytosis pathway. Endocytosis is required for the amyloidogenic processing of the amyloid precursor protein (APP) and thus to initiate the release of the neurotoxic β-amyloid peptide (Aβ), the major component of extracellular plaques found in the brains of Alzheimer's disease patients. Here, we report that small interference RNA-mediated downregulation of flotillin-2 impairs the endocytosis of APP, in both neuroblastoma cells and primary cultures of hippocampal neurons, and reduces the production of Aβ. Similar to tetanus neurotoxin endocytosis, but unlike the internalization of transferrin, clathrin-dependent endocytosis of APP requires cholesterol and adaptor protein-2 but is independent of epsin1 function. Moreover, on a nanoscale resolution using stimulated emission depletion microscopy and by Förster resonance energy transfer with fluorescence lifetime imaging microscopy, we provide evidence that flotillin-2 promotes the clustering of APP at the cell surface. We show that the interaction of flotillin-2 with APP is dependent on cholesterol and that clustering of APP enhances its endocytosis rate. Together, our data suggest that cholesterol/flotillin-dependent clustering of APP may stimulate the internalization into a specialized clathrin-dependent endocytosis pathway to promote amyloidogenic processing.
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Cites
Soluble protein oligomers in neurodegeneration: lessons from the Alzheimer's amyloid β-peptide
Haass, C., & Selkoe, D. J. (2007) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2101 · Cited by 4,744
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Curvature of clathrin-coated pits driven by epsin
Ford, M. G. J., Mills, I. G., Peter, B. J., Vallis, Y., Praefcke, G. J. K., Evans, P. R., & McMahon, H. T. (2002) · Nature · doi:10.1038/nature01020 · Cited by 1,019
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Association of γ-Secretase with Lipid Rafts in Post-Golgi and Endosome Membranes
Vetrivel, K. S., Cheng, H., Lin, W., Sakurai, T., Li, T., Nukina, N., Wong, P. C., Xu, H., & Thinakaran, G. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m407986200 · Cited by 413
Cordy, J. M., Hussain, I., Dingwall, C., Hooper, N. M., & Turner, A. J. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1635130100 · Cited by 356
Cataldo, A. M., Petanceska, S., Peterhoff, C. M., Terio, N. B., Epstein, C. J., Villar, A., Carlson, E. J., Staufenbiel, M., & Nixon, R. A. (2003) · The Journal of Neuroscience · doi:10.1523/jneurosci.23-17-06788.2003 · Cited by 241 · cited 2×
“…the neuronal sortilin-related receptor, Sorl1, a protein involved in the regulation of the endosomal trafficking of APP (Spoelgen et al., 2006; Rogaeva et al., 2007) and the known endocytic pathway abnormalities in Alzheimer’s disease (Cataldo et al., 2003; Nixon, 2005; Laifenfeld et al., 2007).”
BackgroundPietrzik, C. U., Busse, T., Merriam, D. E., Weggen, S., & Koo, E. H. (2002) · The EMBO Journal · doi:10.1093/emboj/cdf568 · Cited by 198
Cited by
Doherty, G. J., & McMahon, H. T. (2009) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.78.081307.110540 · Cited by 3,075
Linking lipids to Alzheimer's disease: cholesterol and beyond
Di Paolo, G., & Kim, T.-W. (2011) · Nature Reviews Neuroscience · doi:10.1038/nrn3012 · Cited by 972
Stimulated Emission Depletion Microscopy
Blom, H., & Widengren, J. (2017) · Chemical Reviews · doi:10.1021/acs.chemrev.6b00653 · Cited by 339
Vassar, R., Kuhn, P., Haass, C., Kennedy, M. E., Rajendran, L., Wong, P. C., & Lichtenthaler, S. F. (2014) · Journal of Neurochemistry · doi:10.1111/jnc.12715 · Cited by 311
Self-citationEmerging Roles of Extracellular Vesicles in the Nervous System
Rajendran, L., Bali, J., Barr, M. M., Court, F. A., Krämer-Albers, E.-M., Picou, F., Raposo, G., van der Vos, K. E., van Niel, G., Wang, J., et al. (2014) · The Journal of Neuroscience · doi:10.1523/jneurosci.3258-14.2014 · Cited by 292
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Metadata
- Authors
- Schneider, A., Rajendran, L., Honsho, M., Gralle, M., Donnert, G., Wouters, F., Hell, S. W., & Simons, M.
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2008-03-12
- Volume
- 28
- Issue
- 11
- Pages
- 2874-2882
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- OpenAlex
- W2054615702
- Cited by
- 210
- References
- 8
- FWCI
- 10.46
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Schneider, A., Rajendran, L., Honsho, M., Gralle, M., Donnert, G., Wouters, F., Hell, S. W., & Simons, M. (2008). Flotillin-Dependent Clustering of the Amyloid Precursor Protein Regulates Its Endocytosis and Amyloidogenic Processing in Neurons. The Journal of Neuroscience. https://doi.org/10.1523/jneurosci.5345-07.2008
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