The DOI matches its Crossref record; 5 of the 5 references it cites were found in a registry or an index.
The discrepancy between presenilin subcellular localization and γ-secretase processing of amyloid precursor protein
Open accessAbstract
We investigated the relationship between PS1 and γ-secretase processing of amyloid precursor protein (APP) in primary cultures of neurons. Increasing the amount of APP at the cell surface or towards endosomes did not significantly affect PS1-dependent γ-secretase cleavage, although little PS1 is present in those subcellular compartments. In contrast, almost no γ-secretase processing was observed when holo-APP or APP-C99, a direct substrate for γ-secretase, were specifically retained in the endoplasmic reticulum (ER) by a double lysine retention motif. Nevertheless, APP-C99-dilysine (KK) colocalized with PS1 in the ER. In contrast, APP-C99 did not colocalize with PS1, but was efficiently processed by PS1-dependent γ-secretase. APP-C99 resides in a compartment that is negative for ER, intermediate compartment, and Golgi marker proteins. We conclude that γ-secretase cleavage of APP-C99 occurs in a specialized subcellular compartment where little or no PS1 is detected. This suggests that at least one other factor than PS1, located downstream of the ER, is required for the γ-cleavage of APP-C99. In agreement, we found that intracellular γ-secretase processing of APP-C99-KK both at the γ40 and the γ42 site could be restored partially after brefeldin A treatment. Our data confirm the “spatial paradox” and raise several questions regarding the PS1 is γ-secretase hypothesis.
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Cites
Vassar, R., Bennett, B. D., Babu-Khan, S., Kahn, S., Mendiaz, E. A., Denis, P., Teplow, D. B., Ross, S., Amarante, P., Loeloff, R., et al. (1999) · Science · doi:10.1126/science.286.5440.735 · Cited by 3,876 · cited 2×
“It is an aspartyl protease cleaving APP at the NH 2 terminus of the amyloid peptide sequence (Vassar et al., 1999).”
BackgroundDeficiency of presenilin-1 inhibits the normal cleavage of amyloid precursor protein
De Strooper, B., Saftig, P., Craessaerts, K., Vanderstichele, H., Guhde, G., Annaert, W., Von Figura, K., & Van Leuven, F. (1998) · Nature · doi:10.1038/34910 · Cited by 1,818
Self-citationEffects of PS1 Deficiency on Membrane Protein Trafficking in Neurons
Naruse, S., Thinakaran, G., Luo, J.-J., Kusiak, J. W., Tomita, T., Iwatsubo, T., Qian, X., Ginty, D. D., Price, D. L., Borchelt, D. R., et al. (1998) · Neuron · doi:10.1016/s0896-6273(00)80637-6 · Cited by 355 · cited 2×
“…activities are also involved in the processing of other integral membrane proteins like Notch and APLP-1 (De Strooper et al., 1999; Naruse et al., 1998; Address correspondence to Wim Annaert and Bart De Strooper, Center for Human Genetics, Neuronal Cell Biology Group, Herestraat…”
BackgroundIntracellular Generation and Accumulation of Amyloid β-Peptide Terminating at Amino Acid 42
Wild-Bode, C., Yamazaki, T., Capell, A., Leimer, U., Steiner, H., Ihara, Y., & Haass, C. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.26.16085 · Cited by 303
Standardization of measurement of β-amyloid(1-42)in cerebrospinal fluid and plasma
Vanderstichele, H., Kerschaver, E. V., Hesse, C., Davidsson, P., Buyse, M.-A., Andreasen, N., Minthon, L., Wallin, A., Blennow, K., & Vanmechelen, E. (2000) · Amyloid · doi:10.3109/13506120009146438 · Cited by 301
Self-citation
Cited by
Trafficking and Proteolytic Processing of APP
Haass, C., Kaether, C., Thinakaran, G., & Sisodia, S. (2012) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a006270 · Cited by 1,075
APP processing in Alzheimer’s disease.
Zhang, Y.-W., Thompson, R., Zhang, H., & Xu, H. (2011) · Molecular Brain · doi:10.1186/1756-6606-4-3 · Cited by 983
Macroautophagy—a novel β-amyloid peptide-generating pathway activated in Alzheimer's disease
Yu, W. H., Cuervo, A. M., Kumar, A., Peterhoff, C. M., Schmidt, S. D., Lee, J.-H., Mohan, P. S., Mercken, M., Farmery, M. R., Tjernberg, L. O., et al. (2005) · The Journal of Cell Biology · doi:10.1083/jcb.200505082 · Cited by 967
Autophagy, amyloidogenesis and Alzheimer disease
Nixon, R. A. (2007) · Journal of Cell Science · doi:10.1242/jcs.019265 · Cited by 749
Upregulated function of mitochondria‐associated ER membranes in Alzheimer disease
Area‐Gomez, E., del Carmen Lara Castillo, M., Tambini, M. D., Guardia‐Laguarta, C., de Groof, A. J. C., Madra, M., Ikenouchi, J., Umeda, M., Bird, T. D., Sturley, S. L., et al. (2012) · The EMBO Journal · doi:10.1038/emboj.2012.202 · Cited by 638
Metadata
- Authors
- Cupers, P., Bentahir, M., Craessaerts, K., Orlans, I., Vanderstichele, H., Saftig, P., De Strooper, B., & Annaert, W.
- Venue
- The Journal of Cell Biology
- Publisher
- Rockefeller University Press
- Published
- 2001-08-13
- Volume
- 154
- Issue
- 4
- Pages
- 731-740
- ISSN
- 0021-9525 (ISSN-L)
- 1540-8140
- OpenAlex
- W2005017513
- Cited by
- 158
- References
- 5
- FWCI
- 12.53
- Type
- journal article
- Language
- en
- Open access
- green
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- Cupers, P., Bentahir, M., Craessaerts, K., Orlans, I., Vanderstichele, H., Saftig, P., De Strooper, B., & Annaert, W. (2001). The discrepancy between presenilin subcellular localization and γ-secretase processing of amyloid precursor protein. The Journal of Cell Biology. https://doi.org/10.1083/jcb.200104045
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