Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents

This Article Full Text Full Text (PDF, 935K) PPT slides of all figures Alert me when this article is cited Citation Map Services Email this article Similar articles in this journal Similar articles in PubMed Alert me to new content in the JCB Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Annaert, W. G. Articles by De Strooper, B. Search for Related Content PubMed PubMed Citation Articles by Annaert, W. G. Articles by De Strooper, B. Related Collections Related Article Social Bookmarking                            What's this?

© The Rockefeller University Press, 0021-9525/1999//277 $5.00
The Journal of Cell Biology, Volume 147, Number 2, , 1999 277-294

Presenilin 1 Controls -Secretase Processing of Amyloid Precursor Protein in Pre-Golgi Compartments of Hippocampal Neurons

^a CME/VIB4/KULeuven, Gasthuisberg, B-3000 Leuven, Belgium
^b Center for Research in Neurodegenerative Diseases, Department of Medical Biophysics and Medicine (Neurology), University of Toronto, Ontario, Canada, M5S 3H2
^c Scios Inc., Sunnyvale, California 94086
Neuronal Cell Biology and Gene Transfer Laboratory, Center for Human Genetics, Flanders Interuniversity Institute for Biotechnology, Gasthuisberg, KULeuven, Herestraat 49, B-3000 Leuven, Belgium.132-16-347181132-16-346227

bart.destrooper{at}med.kuleuven.ac.be

Mutations of presenilin 1 (PS1) causing Alzheimer's disease selectively increase the secretion of the amyloidogenic βA4(1-42), whereas knocking out the gene results in decreased production of both βA4(1-40) and (1-42) amyloid peptides (De Strooper et al. 1998). Therefore, PS1 function is closely linked to the -secretase processing of the amyloid precursor protein (APP). Given the ongoing controversy on the subcellular localization of PS1, it remains unclear at what level of the secretory and endocytic pathways PS1 exerts its activity on APP and on the APP carboxy-terminal fragments that are the direct substrates for -secretase. Therefore, we have reinvestigated the subcellular localization of endogenously expressed PS1 in neurons in vitro and in vivo using confocal microscopy and fine-tuned subcellular fractionation. We show that uncleaved PS1 holoprotein is recovered in the nuclear envelope fraction, whereas the cleaved PS fragments are found mainly in post-ER membranes including the intermediate compartment (IC). PS1 is concentrated in discrete sec23p- and p58/ERGIC-53–positive patches, suggesting its localization in subdomains involved in ER export. PS1 is not found to significant amounts beyond the cis-Golgi. Surprisingly, we found that APP carboxy-terminal fragments also coenrich in the pre-Golgi membrane fractions, consistent with the idea that these fragments are the real substrates for -secretase. Functional evidence that PS1 exerts its effects on -secretase processing of APP in the ER/IC was obtained using a series of APP trafficking mutants. These mutants were investigated in hippocampal neurons derived from transgenic mice expressing PS1wt or PS1 containing clinical mutations (PS1_M146L and PS1_L286V) at physiologically relevant levels. We demonstrate that the APP-London and PS1 mutations have additive effects on the increased secretion of βA4(1-42) relative to βA4(1-40), indicating that both mutations operate independently. Overall, our data clearly establish that PS1 controls ₄₂-secretase activity in pre-Golgi compartments. We discuss models that reconcile this conclusion with the effects of PS1 deficiency on the generation of βA4(1-40) peptide in the late biosynthetic and endocytic pathways.

Key Words: Alzheimer's disease • presenilin 1 • APP processing • hippocampal neuron • -secretase

© 1999 The Rockefeller University Press

CiteULike

Complore

Connotea

Del.icio.us

Digg

Facebook

Reddit

Technorati

Twitter

This article has been cited by other articles:

• Area-Gomez, E., de Groof, A. J.C., Boldogh, I., Bird, T. D., Gibson, G. E., Koehler, C. M., Yu, W. H., Duff, K. E., Yaffe, M. P., Pon, L. A., Schon, E. A. (2009). Presenilins Are Enriched in Endoplasmic Reticulum Membranes Associated with Mitochondria. Am. J. Pathol. 175: 1810-1816 [Abstract] [Full Text]  
• Goodger, Z. V., Rajendran, L., Trutzel, A., Kohli, B. M., Nitsch, R. M., Konietzko, U. (2009). Nuclear signaling by the APP intracellular domain occurs predominantly through the amyloidogenic processing pathway. J. Cell Sci. 122: 3703-3714 [Abstract] [Full Text]  
• Laky, K., Annaert, W., Fowlkes, B. J. (2009). Amyloid precursor family proteins are expressed by thymic and lymph node stromal cells but are not required for lymphocyte development. Int Immunol 21: 1163-1174 [Abstract] [Full Text]  
• Inoue, E., Deguchi-Tawarada, M., Togawa, A., Matsui, C., Arita, K., Katahira-Tayama, S., Sato, T., Yamauchi, E., Oda, Y., Takai, Y. (2009). Synaptic activity prompts {gamma}-secretase-mediated cleavage of EphA4 and dendritic spine formation. JCB 185: 551-564 [Abstract] [Full Text]  
• Muresan, V., Varvel, N. H., Lamb, B. T., Muresan, Z. (2009). The Cleavage Products of Amyloid-{beta} Precursor Protein Are Sorted to Distinct Carrier Vesicles That Are Independently Transported within Neurites. J. Neurosci. 29: 3565-3578 [Abstract] [Full Text]  
• Silveyra, M.-X., Evin, G., Montenegro, M.-F., Vidal, C. J., Martinez, S., Culvenor, J. G., Saez-Valero, J. (2008). Presenilin 1 Interacts with Acetylcholinesterase and Alters Its Enzymatic Activity and Glycosylation. Mol. Cell. Biol. 28: 2908-2919 [Abstract] [Full Text]  
• Spasic, D., Annaert, W. (2008). Building {gamma}-secretase - the bits and pieces. J. Cell Sci. 121: 413-420 [Abstract] [Full Text]  
• Anandatheerthavarada, H. K., Devi, L. (2007). Amyloid Precursor Protein and Mitochondrial Dysfunction in Alzheimer's Disease. Neuroscientist 13: 626-638 [Abstract]  
• Marron, M. B., Singh, H., Tahir, T. A., Kavumkal, J., Kim, H.-Z., Koh, G. Y., Brindle, N. P. J. (2007). Regulated Proteolytic Processing of Tie1 Modulates Ligand Responsiveness of the Receptor-tyrosine Kinase Tie2. J. Biol. Chem. 282: 30509-30517 [Abstract] [Full Text]  
• Uemura, K., Kuzuya, A., Shimozono, Y., Aoyagi, N., Ando, K., Shimohama, S., Kinoshita, A. (2007). GSK3beta Activity Modifies the Localization and Function of Presenilin 1. J. Biol. Chem. 282: 15823-15832 [Abstract] [Full Text]  
• Spasic, D., Raemaekers, T., Dillen, K., Declerck, I., Baert, V., Serneels, L., Fullekrug, J., Annaert, W. (2007). Rer1p competes with APH-1 for binding to nicastrin and regulates {gamma}-secretase complex assembly in the early secretory pathway. JCB 176: 629-640 [Abstract] [Full Text]  
• Spasic, D., Tolia, A., Dillen, K., Baert, V., De Strooper, B., Vrijens, S., Annaert, W. (2006). Presenilin-1 Maintains a Nine-Transmembrane Topology throughout the Secretory Pathway. J. Biol. Chem. 281: 26569-26577 [Abstract] [Full Text]  
• Oh, Y. S., Turner, R. J. (2005). Evidence that the COOH terminus of human presenilin 1 is located in extracytoplasmic space. Am. J. Physiol. Cell Physiol. 289: C576-C581 [Abstract] [Full Text]  
• Zhang, Y.-w., Luo, W.-j., Wang, H., Lin, P., Vetrivel, K. S., Liao, F., Li, F., Wong, P. C., Farquhar, M. G., Thinakaran, G., Xu, H. (2005). Nicastrin Is Critical for Stability and Trafficking but Not Association of Other Presenilin/{gamma}-Secretase Components. J. Biol. Chem. 280: 17020-17026 [Abstract] [Full Text]  
• Kim, J., Hamamoto, S., Ravazzola, M., Orci, L., Schekman, R. (2005). Uncoupled Packaging of Amyloid Precursor Protein and Presenilin 1 into Coat Protein Complex II Vesicles. J. Biol. Chem. 280: 7758-7768 [Abstract] [Full Text]  
• Capell, A., Beher, D., Prokop, S., Steiner, H., Kaether, C., Shearman, M. S., Haass, C. (2005). {gamma}-Secretase Complex Assembly within the Early Secretory Pathway. J. Biol. Chem. 280: 6471-6478 [Abstract] [Full Text]  
• Chyung, J. H., Raper, D. M., Selkoe, D. J. (2005). {gamma}-Secretase Exists on the Plasma Membrane as an Intact Complex That Accepts Substrates and Effects Intramembrane Cleavage. J. Biol. Chem. 280: 4383-4392 [Abstract] [Full Text]  
• Tarassishin, L., Yin, Y. I., Bassit, B., Li, Y.-M. (2004). Processing of Notch and amyloid precursor protein by {gamma}-secretase is spatially distinct. Proc. Natl. Acad. Sci. USA 101: 17050-17055 [Abstract] [Full Text]  
• Khvotchev, M., Sudhof, T. C. (2004). Proteolytic Processing of Amyloid-{beta} Precursor Protein by Secretases Does Not Require Cell Surface Transport. J. Biol. Chem. 279: 47101-47108 [Abstract] [Full Text]  
• Breuza, L., Halbeisen, R., Jeno, P., Otte, S., Barlowe, C., Hong, W., Hauri, H.-P. (2004). Proteomics of Endoplasmic Reticulum-Golgi Intermediate Compartment (ERGIC) Membranes from Brefeldin A-treated HepG2 Cells Identifies ERGIC-32, a New Cycling Protein That Interacts with Human Erv46. J. Biol. Chem. 279: 47242-47253 [Abstract] [Full Text]  
• Esselens, C., Oorschot, V., Baert, V., Raemaekers, T., Spittaels, K., Serneels, L., Zheng, H., Saftig, P., De Strooper, B., Klumperman, J., Annaert, W. (2004). Presenilin 1 mediates the turnover of telencephalin in hippocampal neurons via an autophagic degradative pathway. JCB 166: 1041-1054 [Abstract] [Full Text]  
• Wang, H., Luo, W.-j., Zhang, Y.-w., Li, Y.-M., Thinakaran, G., Greengard, P., Xu, H. (2004). Presenilins and {gamma}-Secretase Inhibitors Affect Intracellular Trafficking and Cell Surface Localization of the {gamma}-Secretase Complex Components. J. Biol. Chem. 279: 40560-40566 [Abstract] [Full Text]  
• Gupta-Rossi, N., Six, E., LeBail, O., Logeat, F., Chastagner, P., Olry, A., Israel, A., Brou, C. (2004). Monoubiquitination and endocytosis direct {gamma}-secretase cleavage of activated Notch receptor. JCB 166: 73-83 [Abstract] [Full Text]  
• Laudon, H., Karlstrom, H., Mathews, P. M., Farmery, M. R., Gandy, S. E., Lundkvist, J., Lendahl, U., Naslund, J. (2004). Functional Domains in Presenilin 1: THE TYR-288 RESIDUE CONTROLS {gamma}-SECRETASE ACTIVITY AND ENDOPROTEOLYSIS. J. Biol. Chem. 279: 23925-23932 [Abstract] [Full Text]  
• Appenzeller-Herzog, C., Roche, A.-C., Nufer, O., Hauri, H.-P. (2004). pH-induced Conversion of the Transport Lectin ERGIC-53 Triggers Glycoprotein Release. J. Biol. Chem. 279: 12943-12950 [Abstract] [Full Text]  
• Wilhelmsen, K., van der Geer, P. (2004). Phorbol 12-Myristate 13-Acetate-Induced Release of the Colony-Stimulating Factor 1 Receptor Cytoplasmic Domain into the Cytosol Involves Two Separate Cleavage Events. Mol. Cell. Biol. 24: 454-464 [Abstract] [Full Text]  
• Schulz, J. G., Annaert, W., Vandekerckhove, J., Zimmermann, P., De Strooper, B., David, G. (2003). Syndecan 3 Intramembrane Proteolysis Is Presenilin/{gamma}-Secretase-dependent and Modulates Cytosolic Signaling. J. Biol. Chem. 278: 48651-48657 [Abstract] [Full Text]  
• Nyabi, O., Bentahir, M., Horre, K., Herreman, A., Gottardi-Littell, N., Van Broeckhoven, C., Merchiers, P., Spittaels, K., Annaert, W., De Strooper, B. (2003). Presenilins Mutated at Asp-257 or Asp-385 Restore Pen-2 Expression and Nicastrin Glycosylation but Remain Catalytically Inactive in the Absence of Wild Type Presenilin. J. Biol. Chem. 278: 43430-43436 [Abstract] [Full Text]  
• Lee, M.-S., Kao, S.-C., Lemere, C. A., Xia, W., Tseng, H.-C., Zhou, Y., Neve, R., Ahlijanian, M. K., Tsai, L.-H. (2003). APP processing is regulated by cytoplasmic phosphorylation. JCB 163: 83-95 [Abstract] [Full Text]  
• Grbovic, O. M., Mathews, P. M., Jiang, Y., Schmidt, S. D., Dinakar, R., Summers-Terio, N. B., Ceresa, B. P., Nixon, R. A., Cataldo, A. M. (2003). Rab5-stimulated Up-regulation of the Endocytic Pathway Increases Intracellular {beta}-Cleaved Amyloid Precursor Protein Carboxyl-terminal Fragment Levels and A{beta} Production. J. Biol. Chem. 278: 31261-31268 [Abstract] [Full Text]  
• Pigino, G., Morfini, G., Pelsman, A., Mattson, M. P., Brady, S. T., Busciglio, J. (2003). Alzheimer's Presenilin 1 Mutations Impair Kinesin-Based Axonal Transport. J. Neurosci. 23: 4499-4508 [Abstract] [Full Text]  
• Grimm, H. S., Beher, D., Lichtenthaler, S. F., Shearman, M. S., Beyreuther, K., Hartmann, T. (2003). gamma -Secretase Cleavage Site Specificity Differs for Intracellular and Secretory Amyloid beta. J. Biol. Chem. 278: 13077-13085 [Abstract] [Full Text]  
• Gassen, G. V., Annaert, W. (2003). Amyloid, Presenilins, and Alzheimer's Disease. Neuroscientist 9: 117-126 [Abstract]  
• Herreman, A., Van Gassen, G., Bentahir, M., Nyabi, O., Craessaerts, K., Mueller, U., Annaert, W., De Strooper, B. (2003). {gamma}-Secretase activity requires the presenilin-dependent trafficking of nicastrin through the Golgi apparatus but not its complex glycosylation. J. Cell Sci. 116: 1127-1136 [Abstract] [Full Text]  
• Luo, W.-j., Wang, H., Li, H., Kim, B. S., Shah, S., Lee, H.-J., Thinakaran, G., Kim, T.-W., Yu, G., Xu, H. (2003). PEN-2 and APH-1 Coordinately Regulate Proteolytic Processing of Presenilin 1. J. Biol. Chem. 278: 7850-7854 [Abstract] [Full Text]  
• Komano, H., Shiraishi, H., Kawamura, Y., Sai, X., Suzuki, R., Serneels, L., Kawaichi, M., Kitamura, T., Yanagisawa, K. (2002). A New Functional Screening System for Identification of Regulators for the Generation of Amyloid beta -Protein. J. Biol. Chem. 277: 39627-39633 [Abstract] [Full Text]  
• Hartmann, D., de Strooper, B., Serneels, L., Craessaerts, K., Herreman, A., Annaert, W., Umans, L., Lubke, T., Lena Illert, A., von Figura, K., Saftig, P. (2002). The disintegrin/metalloprotease ADAM 10 is essential for Notch signalling but not for {alpha}-secretase activity in fibroblasts. Hum Mol Genet 11: 2615-2624 [Abstract] [Full Text]  
• Bazan, N. G., Lukiw, W. J. (2002). Cyclooxygenase-2 and Presenilin-1 Gene Expression Induced by Interleukin-1beta and Amyloid beta 42 Peptide Is Potentiated by Hypoxia in Primary Human Neural Cells. J. Biol. Chem. 277: 30359-30367 [Abstract] [Full Text]  
• Kaether, C., Lammich, S., Edbauer, D., Ertl, M., Rietdorf, J., Capell, A., Steiner, H., Haass, C. (2002). Presenilin-1 affects trafficking and processing of {beta}APP and is targeted in a complex with nicastrin to the plasma membrane. JCB 158: 551-561 [Abstract] [Full Text]  
• Oorschot, V., de Wit, H., Annaert, W. G., Klumperman, J. (2002). A Novel Flat-embedding Method to Prepare Ultrathin Cryosections from Cultured Cells in Their In Situ Orientation. J. Histochem. Cytochem. 50: 1067-1080 [Abstract] [Full Text]  
• Yang, D.-S., Tandon, A., Chen, F., Yu, G., Yu, H., Arawaka, S., Hasegawa, H., Duthie, M., Schmidt, S. D., Ramabhadran, T. V., Nixon, R. A., Mathews, P. M., Gandy, S. E., Mount, H. T. J., St George-Hyslop, P., Fraser, P. E. (2002). Mature Glycosylation and Trafficking of Nicastrin Modulate Its Binding to Presenilins. J. Biol. Chem. 277: 28135-28142 [Abstract] [Full Text]  
• Edbauer, D., Winkler, E., Haass, C., Steiner, H. (2002). Presenilin and nicastrin regulate each other and determine amyloid beta -peptide production via complex formation. Proc. Natl. Acad. Sci. USA 99: 8666-8671 [Abstract] [Full Text]  
• Runz, H., Rietdorf, J., Tomic, I., de Bernard, M., Beyreuther, K., Pepperkok, R., Hartmann, T. (2002). Inhibition of Intracellular Cholesterol Transport Alters Presenilin Localization and Amyloid Precursor Protein Processing in Neuronal Cells. J. Neurosci. 22: 1679-1689 [Abstract] [Full Text]  
• Capell, A., Meyn, L., Fluhrer, R., Teplow, D. B., Walter, J., Haass, C. (2002). Apical Sorting of beta -Secretase Limits Amyloid beta -Peptide Production. J. Biol. Chem. 277: 5637-5643 [Abstract] [Full Text]  
• Killick, R., Pollard, C. C., Asuni, A. A., Mudher, A. K., Richardson, J. C., Rupniak, H. T., Sheppard, P. W., Varndell, I. M., Brion, J.-P., Levey, A. I., Levy, O. A., Vestling, M., Cowburn, R., Lovestone, S., Anderton, B. H. (2001). Presenilin 1 Independently Regulates beta -Catenin Stability and Transcriptional Activity. J. Biol. Chem. 276: 48554-48561 [Abstract] [Full Text]  
• Yu, C., Kim, S.-H., Ikeuchi, T., Xu, H., Gasparini, L., Wang, R., Sisodia, S. S. (2001). Characterization of a Presenilin-mediated Amyloid Precursor Protein Carboxyl-terminal Fragment gamma . EVIDENCE FOR DISTINCT MECHANISMS INVOLVED IN gamma -SECRETASE PROCESSING OF THE APP AND Notch1 TRANSMEMBRANE DOMAINS. J. Biol. Chem. 276: 43756-43760 [Abstract] [Full Text]  
• Wiltfang, J., Esselmann, H., Cupers, P., Neumann, M., Kretzschmar, H., Beyermann, M., Schleuder, D., Jahn, H., Ruther, E., Kornhuber, J., Annaert, W., De Strooper, B., Saftig, P. (2001). Elevation of beta -Amyloid Peptide 2-42 in Sporadic and Familial Alzheimer's Disease and Its Generation in PS1 Knockout Cells. J. Biol. Chem. 276: 42645-42657 [Abstract] [Full Text]  
• Kim, S.-H., Leem, J. Y., Lah, J. J., Slunt, H. H., Levey, A. I., Thinakaran, G., Sisodia, S. S. (2001). Multiple Effects of Aspartate Mutant Presenilin 1 on the Processing and Trafficking of Amyloid Precursor Protein. J. Biol. Chem. 276: 43343-43350 [Abstract] [Full Text]  
• Esler, W. P., Wolfe, M. S. (2001). A Portrait of Alzheimer Secretases--New Features and Familiar Faces. Science 293: 1449-1454 [Abstract] [Full Text]  
• De Jonghe, C., Esselens, C., Kumar-Singh, S., Craessaerts, K., Serneels, S., Checler, F., Annaert, W., Van Broeckhoven, C., De Strooper, B. (2001). Pathogenic APP mutations near the {gamma}-secretase cleavage site differentially affect A{beta} secretion and APP C-terminal fragment stability. Hum Mol Genet 10: 1665-1671 [Abstract] [Full Text]  
• Stephan, A., Laroche, S., Davis, S. (2001). Generation of Aggregated {beta}-Amyloid in the Rat Hippocampus Impairs Synaptic Transmission and Plasticity and Causes Memory Deficits. J. Neurosci. 21: 5703-5714 [Abstract] [Full Text]  
• Selkoe, D. J. (2001). Alzheimer's Disease: Genes, Proteins, and Therapy. Physiol. Rev. 81: 741-766 [Abstract] [Full Text]  
• Soriano, S., Kang, D. E., Fu, M., Pestell, R., Chevallier, N., Zheng, H., Koo, E. H. (2001). Presenilin 1 Negatively Regulates {beta}-Catenin/T Cell Factor/Lymphoid Enhancer Factor-1 Signaling Independently of {beta}-Amyloid Precursor Protein and Notch Processing. JCB 152: 785-794 [Abstract] [Full Text]  
• Pigino, G., Pelsman, A., Mori, H., Busciglio, J. (2001). Presenilin-1 Mutations Reduce Cytoskeletal Association, Deregulate Neurite Growth, and Potentiate Neuronal Dystrophy and Tau Phosphorylation. J. Neurosci. 21: 834-842 [Abstract] [Full Text]  
• Tesseur, I., Van Dorpe, J., Bruynseels, K., Bronfman, F., Sciot, R., Van Lommel, A., Van Leuven, F. (2000). Prominent Axonopathy and Disruption of Axonal Transport in Transgenic Mice Expressing Human Apolipoprotein E4 in Neurons of Brain and Spinal Cord. Am. J. Pathol. 157: 1495-1510 [Abstract] [Full Text]  
• Ueda, J., Wentz–Hunter, K. K., Cheng, E. L., Fukuchi, T., Abe, H., Yue, B. Y.J.T. (2000). Ultrastructural Localization of Myocilin in Human Trabecular Meshwork Cells and Tissues. J. Histochem. Cytochem. 48: 1321-1330 [Abstract] [Full Text]  
• Devi, G., Fotiou, A., Jyrinji, D., Tycko, B., DeArmand, S., Rogaeva, E., Song, Y.-Q., Medieros, H., Liang, Y., Orlacchio, A., Williamson, J., St George-Hyslop, P., Mayeux, R. (2000). Novel Presenilin 1 Mutations Associated With Early Onset of Dementia in a Family With Both Early-Onset and Late-Onset Alzheimer Disease. Arch Neurol 57: 1454-1457 [Abstract] [Full Text]  
• Xia, W., Ray, W. J., Ostaszewski, B. L., Rahmati, T., Kimberly, W. T., Wolfe, M. S., Zhang, J., Goate, A. M., Selkoe, D. J. (2000). Presenilin complexes with the C-terminal fragments of amyloid precursor protein at the sites of amyloid beta -protein generation. Proc. Natl. Acad. Sci. USA 97: 9299-9304 [Abstract] [Full Text]  
• De Strooper, B, Annaert, W (2000). Proteolytic processing and cell biological functions of the amyloid precursor protein. J. Cell Sci. 113: 1857-1870 [Abstract]  
• Hauri, H., Kappeler, F, Andersson, H, Appenzeller, C (2000). ERGIC-53 and traffic in the secretory pathway. J. Cell Sci. 113: 587-596 [Abstract]  
• Haass, C., Strooper, B. D. (1999). The Presenilins in Alzheimer's Disease--Proteolysis Holds the Key. Science 286: 916-919 [Abstract] [Full Text]  
• Verdile, G., Martins, R. N., Duthie, M., Holmes, E., St George-Hyslop, P. H., Fraser, P. E. (2000). Inhibiting Amyloid Precursor Protein C-terminal Cleavage Promotes an Interaction with Presenilin 1. J. Biol. Chem. 275: 20794-20798 [Abstract] [Full Text]  
• Pinnix, I., Musunuru, U., Tun, H., Sridharan, A., Golde, T., Eckman, C., Ziani-Cherif, C., Onstead, L., Sambamurti, K. (2001). A Novel gamma -Secretase Assay Based on Detection of the Putative C-terminal Fragment-gamma of Amyloid beta Protein Precursor. J. Biol. Chem. 276: 481-487 [Abstract] [Full Text]  
• Creemers, J. W. M., Ines Dominguez, D., Plets, E., Serneels, L., Taylor, N. A., Multhaup, G., Craessaerts, K., Annaert, W., De Strooper, B. (2001). Processing of beta -Secretase by Furin and Other Members of the Proprotein Convertase Family. J. Biol. Chem. 276: 4211-4217 [Abstract] [Full Text]  
• Chen, F., Yang, D.-S., Petanceska, S., Yang, A., Tandon, A., Yu, G., Rozmahel, R., Ghiso, J., Nishimura, M., Zhang, D. M., Kawarai, T., Levesque, G., Mills, J., Levesque, L., Song, Y.-Q., Rogaeva, E., Westaway, D., Mount, H., Gandy, S., St George-Hyslop, P., Fraser, P. E. (2000). Carboxyl-terminal Fragments of Alzheimer beta -Amyloid Precursor Protein Accumulate in Restricted and Unpredicted Intracellular Compartments in Presenilin 1-deficient Cells. J. Biol. Chem. 275: 36794-36802 [Abstract] [Full Text]  
• Maltese, W. A., Wilson, S., Tan, Y., Suomensaari, S., Sinha, S., Barbour, R., McConlogue, L. (2001). Retention of the Alzheimer's Amyloid Precursor Fragment C99 in the Endoplasmic Reticulum Prevents Formation of Amyloid beta -Peptide. J. Biol. Chem. 276: 20267-20279 [Abstract] [Full Text]  
• Iwata, H., Tomita, T., Maruyama, K., Iwatsubo, T. (2001). Subcellular Compartment and Molecular Subdomain of beta -Amyloid Precursor Protein Relevant to the Abeta 42-promoting Effects of Alzheimer Mutant Presenilin 2. J. Biol. Chem. 276: 21678-21685 [Abstract] [Full Text]  
• Steinhilb, M. L., Turner, R. S., Gaut, J. R. (2001). The Protease Inhibitor, MG132, Blocks Maturation of the Amyloid Precursor Protein Swedish Mutant Preventing Cleavage by beta -Secretase. J. Biol. Chem. 276: 4476-4484 [Abstract] [Full Text]  
• Siman, R., Flood, D. G., Thinakaran, G., Neumar, R. W. (2001). Endoplasmic Reticulum Stress-induced Cysteine Protease Activation in Cortical Neurons. EFFECT OF AN ALZHEIMER'S DISEASE-LINKED PRESENILIN-1 KNOCK-IN MUTATION. J. Biol. Chem. 276: 44736-44743 [Abstract] [Full Text]  
• Wolfe, M. S., Haass, C. (2001). The Role of Presenilins in gamma -Secretase Activity. J. Biol. Chem. 276: 5413-5416 [Full Text]  
• Xia, X., Qian, S., Soriano, S., Wu, Y., Fletcher, A. M., Wang, X.-J., Koo, E. H., Wu, X., Zheng, H. (2001). Loss of presenilin 1 is associated with enhanced beta -catenin signaling and skin tumorigenesis. Proc. Natl. Acad. Sci. USA 98: 10863-10868 [Abstract] [Full Text]  
• 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 {gamma}-secretase processing of amyloid precursor protein. JCB 154: 731-740 [Abstract] [Full Text]  

Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents