Startseite Membrane trafficking and proteolytic activity of γ-secretase in Alzheimer’s disease
Artikel
Lizenziert
Nicht lizenziert Erfordert eine Authentifizierung

Membrane trafficking and proteolytic activity of γ-secretase in Alzheimer’s disease

  • Kunihiko Kanatsu und Taisuke Tomita ORCID logo EMAIL logo
Veröffentlicht/Copyright: 7. Juli 2016

Abstract

γ-Secretase is an intramembrane-cleaving protease that generates various forms of amyloid-β peptides (Aβ) that accumulate in the brains of Alzheimer’s disease (AD) patients. The intracellular trafficking and subcellular localization of γ-secretase are linked to both qualitative and quantitative changes in Aβ production. However, the precise intracellular localization of γ-secretase as well as its detailed regulatory mechanisms have remained elusive. Recent genetic studies on AD provide ample evidence that alteration of the subcellular localization of γ-secretase contributes to the pathogenesis of AD. Here we review our current understanding of the intracellular membrane trafficking of γ-secretase, the association between its localization and proteolytic activity, and the possibility of γ-secretase as a therapeutic target against AD.

Keywords: ; APP; CALM; endocytosis; SORL1

Award Identifier / Grant number: 15H02492

Funding statement: This work was supported in part by a Grant-in-Aid for Scientific Research (A) from the Japan Society for the Promotion of Science (JSPS) (Grant/Award Number: ‘15H02492’), by grants from Takeda Science Foundation, the Cell Science Research Foundation, the Tokyo Biochemical Research Foundation, the Daiichi Sankyo Foundation of Life Science, NAGASE Science Technology Foundation and Ono Medical Research Foundation. K.K. is a research fellow of JSPS.

Acknowledgments

This work was supported in part by a Grant-in-Aid for Scientific Research (A) from the Japan Society for the Promotion of Science (JSPS) (Grant/Award Number: ‘15H02492’), by grants from Takeda Science Foundation, the Cell Science Research Foundation, the Tokyo Biochemical Research Foundation, the Daiichi Sankyo Foundation of Life Science, NAGASE Science Technology Foundation and Ono Medical Research Foundation. K.K. is a research fellow of JSPS.

References

Ahn, K., Shelton, C.C., Tian, Y., Zhang, X., Gilchrist, M.L., Sisodia, S.S., and Li, Y.M. (2010). Activation and intrinsic gamma-secretase activity of presenilin 1. Proc. Natl. Acad Sci. USA 107, 21435–21440.10.1073/pnas.1013246107Suche in Google Scholar PubMed PubMed Central

Andersen, O.M., Reiche, J., Schmidt, V., Gotthardt, M., Spoelgen, R., Behlke, J., von Arnim, C.A., Breiderhoff, T., Jansen, P., Wu, X., et al. (2005). Neuronal sorting protein-related receptor sorLA/LR11 regulates processing of the amyloid precursor protein. Proc. Natl. Acad Sci. USA 102, 13461–13466.10.1073/pnas.0503689102Suche in Google Scholar PubMed PubMed Central

Ayciriex, S., Gerber, H., Osuna, G.M., Chami, M., Stahlberg, H., Shevchenko, A., and Fraering, P.C. (2016). The lipidome associated with the γ-secretase complex is required for its integrity and activity. Biochem. J. 473, 321–334.10.1042/BJ20150448Suche in Google Scholar PubMed

Bai, X.C., Rajendra, E., Yang, G., Shi, Y., and Scheres, S.H. (2015a). Sampling the conformational space of the catalytic subunit of human gamma-secretase. eLife 4, pii: e11182.10.7554/eLife.11182Suche in Google Scholar PubMed PubMed Central

Bai, X.C., Yan, C., Yang, G., Lu, P., Ma, D., Sun, L., Zhou, R., Scheres, S.H., and Shi, Y. (2015b). An atomic structure of human γ-secretase. Nature 525, 212–217.10.1038/nature14892Suche in Google Scholar PubMed PubMed Central

Beher, D., Fricker, M., Nadin, A., Clarke, E.E., Wrigley, J.D., Li, Y.M., Culvenor, J.G., Masters, C.L., Harrison, T., and Shearman, M.S. (2003). In vitro characterization of the presenilin-dependent γ-secretase complex using a novel affinity ligand. Biochemistry 42, 8133–8142.10.1021/bi034045zSuche in Google Scholar PubMed

Bohm, C., Chen, F., Sevalle, J., Qamar, S., Dodd, R., Li, Y., Schmitt-Ulms, G., Fraser, P.E., and St George-Hyslop, P.H. (2015). Current and future implications of basic and translational research on amyloid-beta peptide production and removal pathways. Mol. Cell Neurosci. 66, 3–11.10.1016/j.mcn.2015.02.016Suche in Google Scholar PubMed PubMed Central

Bolduc, D.M., Montagna, D.R., Gu, Y., Selkoe, D.J., and Wolfe, M.S. (2016). Nicastrin functions to sterically hinder γ-secretase-substrate interactions driven by substrate transmembrane domain. Proc. Natl. Acad Sci. USA 113, E509–518.10.1073/pnas.1512952113Suche in Google Scholar PubMed PubMed Central

Charrin, S., Jouannet, S., Boucheix, C., and Rubinstein, E. (2014). Tetraspanins at a glance. J. Cell Sci. 127, 3641–3648.10.1242/jcs.154906Suche in Google Scholar PubMed

Chavez-Gutierrez, L., Tolia, A., Maes, E., Li, T., Wong, P.C., and de Strooper, B. (2008). Glu(332) in the Nicastrin ectodomain is essential for γ-secretase complex maturation but not for its activity. J. Biol. Chem. 283, 20096–20105.10.1074/jbc.M803040200Suche in Google Scholar PubMed

Chen, A.C., Kim, S., Shepardson, N., Patel, S., Hong, S., and Selkoe, D.J. (2015). Physical and functional interaction between the α- and γ-secretases: a new model of regulated intramembrane proteolysis. J. Cell Biol. 211, 1157–1176.10.1083/jcb.201502001Suche in Google Scholar PubMed PubMed Central

Chyung, J.H., Raper, D.M., and 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, 4383–4392.10.1074/jbc.M409272200Suche in Google Scholar PubMed

De Strooper, B. and Chavez Gutierrez, L. (2015). Learning by failing: ideas and concepts to tackle γ-secretases in Alzheimer’s disease and beyond. Annu. Rev. Pharmacol. Toxicol. 55, 419–437.10.1146/annurev-pharmtox-010814-124309Suche in Google Scholar PubMed

De Strooper, B., Iwatsubo, T., and Wolfe, M.S. (2012). Presenilins and γ-secretase: structure, function, and role in Alzheimer disease. Cold Spring Harb. Perspect. Med. 2, a006304.10.1101/cshperspect.a006304Suche in Google Scholar PubMed PubMed Central

Dodson, S.E., Gearing, M., Lippa, C.F., Montine, T.J., Levey, A.I., and Lah, J.J. (2006). LR11/SorLA expression is reduced in sporadic Alzheimer disease but not in familial Alzheimer disease. J. Neuropathol. Exp. Neurol. 65, 866–872.10.1097/01.jnen.0000228205.19915.20Suche in Google Scholar PubMed PubMed Central

Dodson, S.E., Andersen, O.M., Karmali, V., Fritz, J.J., Cheng, D., Peng, J., Levey, A.I., Willnow, T.E., and Lah, J.J. (2008). Loss of LR11/SORLA enhances early pathology in a mouse model of amyloidosis: evidence for a proximal role in Alzheimer’s disease. J. Neurosci. 28, 12877–12886.10.1523/JNEUROSCI.4582-08.2008Suche in Google Scholar PubMed PubMed Central

Dolev, I., Fogel, H., Milshtein, H., Berdichevsky, Y., Lipstein, N., Brose, N., Gazit, N., and Slutsky, I. (2013). Spike bursts increase amyloid-β 40/42 ratio by inducing a presenilin-1 conformational change. Nat. Neurosci. 16, 587–595.10.1038/nn.3376Suche in Google Scholar PubMed

Esler, W.P., Kimberly, W.T., Ostaszewski, B.L., Diehl, T.S., Moore, C.L., Tsai, J.Y., Rahmati, T., Xia, W., Selkoe, D.J., and Wolfe, M.S. (2000). Transition-state analogue inhibitors of γ-secretase bind directly to presenilin-1. Nat. Cell Biol. 2, 428–434.10.1038/35017062Suche in Google Scholar PubMed

Fassler, M., Zocher, M., Klare, S., de la Fuente, A.G., Scheuermann, J., Capell, A., Haass, C., Valkova, C., Veerappan, A., Schneider, D., et al. (2010). Masking of transmembrane-based retention signals controls ER export of γ-secretase. Traffic 11, 250–258.10.1111/j.1600-0854.2009.01014.xSuche in Google Scholar PubMed

Fukumori, A., Okochi, M., Tagami, S., Jiang, J., Itoh, N., Nakayama, T., Yanagida, K., Ishizuka-Katsura, Y., Morihara, T., Kamino, K., et al. (2006). Presenilin-dependent γ-secretase on plasma membrane and endosomes is functionally distinct. Biochemistry 45, 4907–4914.10.1021/bi052412wSuche in Google Scholar PubMed

Funamoto, S., Sasaki, T., Ishihara, S., Nobuhara, M., Nakano, M., Watanabe-Takahashi, M., Saito, T., Kakuda, N., Miyasaka, T., Nishikawa, K., et al. (2013). Substrate ectodomain is critical for substrate preference and inhibition of γ-secretase. Nat. Commun. 4, 2529.10.1038/ncomms3529Suche in Google Scholar PubMed PubMed Central

Gu, Y., Misonou, H., Sato, T., Dohmae, N., Takio, K., and Ihara, Y. (2001). Distinct intramembrane cleavage of the β-amyloid precursor protein family resembling γ-secretase-like cleavage of Notch. J. Biol. Chem. 276, 35235–35238.10.1074/jbc.C100357200Suche in Google Scholar PubMed

Harel, A., Wu, F., Mattson, M.P., Morris, C.M., and Yao, P.J. (2008). Evidence for CALM in directing VAMP2 trafficking. Traffic 9, 417–429.10.1111/j.1600-0854.2007.00694.xSuche in Google Scholar PubMed

Harold, D., Abraham, R., Hollingworth, P., Sims, R., Gerrish, A., Hamshere, M.L., Pahwa, J.S., Moskvina, V., Dowzell, K., Williams, A., et al. (2009). Genome-wide association study identifies variants at CLU and PICALM associated with Alzheimer’s disease. Nat. Genet. 41, 1088–1093.10.1038/ng.440Suche in Google Scholar PubMed PubMed Central

Hayashi, I., Takatori, S., Urano, Y., Miyake, Y., Takagi, J., Sakata-Yanagimoto, M., Iwanari, H., Osawa, S., Morohashi, Y., Li, T., et al. (2012). Neutralization of the γ-secretase activity by monoclonal antibody against extracellular domain of nicastrin. Oncogene 31, 787–798.10.1038/onc.2011.265Suche in Google Scholar PubMed PubMed Central

Hollingworth, P., Harold, D., Sims, R., Gerrish, A., Lambert, J.C., Carrasquillo, M.M., Abraham, R., Hamshere, M.L., Pahwa, J.S., Moskvina, V., et al. (2011). Common variants at ABCA7, MS4A6A/MS4A4E, EPHA1, CD33 and CD2AP are associated with Alzheimer’s disease. Nat. Genet. 43, 429–435.10.1038/ng.803Suche in Google Scholar PubMed PubMed Central

Holmes, O., Paturi, S., Ye, W., Wolfe, M.S., and Selkoe, D.J. (2012). Effects of membrane lipids on the activity and processivity of purified γ-secretase. Biochemistry 51, 3565–3575.10.1021/bi300303gSuche in Google Scholar PubMed PubMed Central

Isoo, N., Sato, C., Miyashita, H., Shinohara, M., Takasugi, N., Morohashi, Y., Tsuji, S., Tomita, T., and Iwatsubo, T. (2007). Aβ42 overproduction associated with structural changes in the catalytic pore of γ-secretase: common effects of Pen-2 N-terminal elongation and fenofibrate. J. Biol. Chem. 282, 12388–12396.10.1074/jbc.M611549200Suche in Google Scholar PubMed

Iwata, H., Tomita, T., Maruyama, K., and Iwatsubo, T. (2001). Subcellular compartment and molecular subdomain of beta-amyloid precursor protein relevant to the Aβ42-promoting effects of Alzheimer mutant presenilin 2. J. Biol. Chem. 276, 21678–21685.10.1074/jbc.M007989200Suche in Google Scholar PubMed

Iwatsubo, T., Odaka, A., Suzuki, N., Mizusawa, H., Nukina, N., and Ihara, Y. (1994). Visualization of Aβ42(43) and Aβ40 in senile plaques with end-specific Aβ monoclonals: evidence that an initially deposited species is Aβ42(43). Neuron 13, 45–53.10.1016/0896-6273(94)90458-8Suche in Google Scholar PubMed

Jarrett, J.T., Berger, E.P., and Lansbury, P.T., Jr. (1993). The carboxy terminus of the β amyloid protein is critical for the seeding of amyloid formation: implications for the pathogenesis of Alzheimer’s disease. Biochemistry 32, 4693–4697.10.1021/bi00069a001Suche in Google Scholar PubMed

Jin, N., Lang, M.J., and Weisman, L.S. (2016). Phosphatidylinositol 3,5-bisphosphate: regulation of cellular events in space and time. Biochem. Soc. Trans. 44, 177–184.10.1042/BST20150174Suche in Google Scholar PubMed PubMed Central

Jorissen, E., Prox, J., Bernreuther, C., Weber, S., Schwanbeck, R., Serneels, L., Snellinx, A., Craessaerts, K., Thathiah, A., Tesseur, I., et al. (2010). The disintegrin/metalloproteinase ADAM10 is essential for the establishment of the brain cortex. J. Neurosci. 30, 4833–4844.10.1523/JNEUROSCI.5221-09.2010Suche in Google Scholar PubMed PubMed Central

Jurisch-Yaksi, N., Rose, A.J., Lu, H., Raemaekers, T., Munck, S., Baatsen, P., Baert, V., Vermeire, W., Scales, S.J., Verleyen, D., et al. (2013). Rer1p maintains ciliary length and signaling by regulating γ-secretase activity and Foxj1a levels. J. Cell Biol. 200, 709–720.10.1083/jcb.201208175Suche in Google Scholar PubMed PubMed Central

Kaether, C., Lammich, S., Edbauer, D., Ertl, M., Rietdorf, J., Capell, A., Steiner, H., and Haass, C. (2002). Presenilin-1 affects trafficking and processing of βAPP and is targeted in a complex with nicastrin to the plasma membrane. J. Cell Biol. 158, 551–561.10.1083/jcb.200201123Suche in Google Scholar PubMed PubMed Central

Kaether, C., Capell, A., Edbauer, D., Winkler, E., Novak, B., Steiner, H., and Haass, C. (2004). The presenilin C-terminus is required for ER-retention, nicastrin-binding and γ-secretase activity. EMBO J. 23, 4738–4748.10.1038/sj.emboj.7600478Suche in Google Scholar PubMed PubMed Central

Kaether, C., Schmitt, S., Willem, M., and Haass, C. (2006). Amyloid precursor protein and Notch intracellular domains are generated after transport of their precursors to the cell surface. Traffic 7, 408–415.10.1111/j.1600-0854.2006.00396.xSuche in Google Scholar PubMed

Kaether, C., Scheuermann, J., Fassler, M., Zilow, S., Shirotani, K., Valkova, C., Novak, B., Kacmar, S., Steiner, H., and Haass, C. (2007). Endoplasmic reticulum retention of the γ-secretase complex component Pen2 by Rer1. EMBO Rep. 8, 743–748.10.1038/sj.embor.7401027Suche in Google Scholar PubMed PubMed Central

Kanatsu, K., Morohashi, Y., Suzuki, M., Kuroda, H., Watanabe, T., Tomita, T., and Iwatsubo, T. (2014). Decreased CALM expression reduces Aβ42 to total Aβ ratio through clathrin-mediated endocytosis of γ-secretase. Nat. Commun. 5, 3386.10.1038/ncomms4386Suche in Google Scholar PubMed

Kanatsu, K., Hori, Y., Takatori, S., Watanabe, T., Iwatsubo, T., and Tomita, T. (2016). Partial loss of CALM function reduces Aβ42 production and amyloid deposition in vivo. Hum. Mol. Genet., in press.10.1093/hmg/ddw239Suche in Google Scholar PubMed

Kim, S.H. and Sisodia, S.S. (2005). Evidence that the “NF” motif in transmembrane domain 4 of presenilin 1 is critical for binding with PEN-2. J. Biol. Chem. 280, 41953–41966.10.1074/jbc.M509070200Suche in Google Scholar PubMed

Kim, J., Kleizen, B., Choy, R., Thinakaran, G., Sisodia, S.S., and Schekman, R.W. (2007). Biogenesis of γ-secretase early in the secretory pathway. J. Cell Biol. 179, 951–963.10.1083/jcb.200709012Suche in Google Scholar PubMed PubMed Central

Kimura, R., Yamamoto, M., Morihara, T., Akatsu, H., Kudo, T., Kamino, K., and Takeda, M. (2009). SORL1 is genetically associated with Alzheimer disease in a Japanese population. Neurosci. Lett. 461, 177–180.10.1016/j.neulet.2009.06.014Suche in Google Scholar PubMed

Koo, E.H. and Squazzo, S.L. (1994). Evidence that production and release of amyloid β-protein involves the endocytic pathway. J. Biol. Chem. 269, 17386–17389.10.1016/S0021-9258(17)32449-3Suche in Google Scholar

Kuhn, P.H., Wang, H., Dislich, B., Colombo, A., Zeitschel, U., Ellwart, J.W., Kremmer, E., Rossner, S., and Lichtenthaler, S.F. (2010). ADAM10 is the physiologically relevant, constitutive α-secretase of the amyloid precursor protein in primary neurons. EMBO J. 29, 3020–3032.10.1038/emboj.2010.167Suche in Google Scholar PubMed PubMed Central

Lambert, J.C., Ibrahim-Verbaas, C.A., Harold, D., Naj, A.C., Sims, R., Bellenguez, C., DeStafano, A.L., Bis, J.C., Beecham, G.W., Grenier-Boley, B., et al. (2013). Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer’s disease. Nat. Genet. 45, 1452–1458.10.1038/ng.2802Suche in Google Scholar PubMed PubMed Central

LaVoie, M.J., Fraering, P.C., Ostaszewski, B.L., Ye, W., Kimberly, W.T., Wolfe, M.S., and Selkoe, D.J. (2003). Assembly of the γ-secretase complex involves early formation of an intermediate subcomplex of Aph-1 and nicastrin. J. Biol. Chem. 278, 37213–37222.10.1074/jbc.M303941200Suche in Google Scholar PubMed

Li, Y.M., Xu, M., Lai, M.T., Huang, Q., Castro, J.L., DiMuzio-Mower, J., Harrison, T., Lellis, C., Nadin, A., Neduvelil, J.G., et al. (2000). Photoactivated γ-secretase inhibitors directed to the active site covalently label presenilin 1. Nature 405, 689–694.10.1038/35015085Suche in Google Scholar PubMed

Liu, F., Arias-Vasquez, A., Sleegers, K., Aulchenko, Y.S., Kayser, M., Sanchez-Juan, P., Feng, B.J., Bertoli-Avella, A.M., van Swieten, J., Axenovich, T.I., et al. (2007). A genomewide screen for late-onset Alzheimer disease in a genetically isolated Dutch population. Am J. Hum. Genet. 81, 17–31.10.1086/518720Suche in Google Scholar PubMed PubMed Central

Liu, X., Zhao, X., Zeng, X., Bossers, K., Swaab, D.F., Zhao, J., and Pei, G. (2013). β-arrestin1 regulates γ-secretase complex assembly and modulates amyloid-β pathology. Cell Res. 23, 351–365.10.1038/cr.2012.167Suche in Google Scholar PubMed PubMed Central

Meckler, X. and Checler, F. (2016). Presenilin 1 and presenilin 2 target γ-secretase complexes to distinct cellular compartments. J. Biol. Chem. 291, 12821–12837.10.1074/jbc.M115.708297Suche in Google Scholar PubMed PubMed Central

Meyerholz, A., Hinrichsen, L., Groos, S., Esk, P.C., Brandes, G., and Ungewickell, E.J. (2005). Effect of clathrin assembly lymphoid myeloid leukemia protein depletion on clathrin coat formation. Traffic 6, 1225–1234.10.1111/j.1600-0854.2005.00355.xSuche in Google Scholar PubMed

Miller, S.E., Sahlender, D.A., Graham, S.C., Honing, S., Robinson, M.S., Peden, A.A., and Owen, D.J. (2011). The molecular basis for the endocytosis of small R-SNAREs by the clathrin adaptor CALM. Cell 147, 1118–1131.10.1016/j.cell.2011.10.038Suche in Google Scholar PubMed PubMed Central

Miller, S.E., Mathiasen, S., Bright, N.A., Pierre, F., Kelly, B.T., Kladt, N., Schauss, A., Merrifield, C.J., Stamou, D., Honing, S., et al. (2015). CALM regulates clathrin-coated vesicle size and maturation by directly sensing and driving membrane curvature. Dev. Cell 33, 163–175.10.1016/j.devcel.2015.03.002Suche in Google Scholar PubMed PubMed Central

Morohashi, Y. and Tomita, T. (2013). Protein trafficking and maturation regulate intramembrane proteolysis. Biochim. Biophys. Acta 1828, 2855–2861.10.1016/j.bbamem.2013.06.001Suche in Google Scholar PubMed

Nelson, C.D. and Sheng, M. (2013). Gpr3 stimulates Aβ production via interactions with APP and β-arrestin2. PLoS One 8, e74680.10.1371/journal.pone.0074680Suche in Google Scholar PubMed PubMed Central

Ni, Y., Zhao, X., Bao, G., Zou, L., Teng, L., Wang, Z., Song, M., Xiong, J., Bai, Y., and Pei, G. (2006). Activation of β2-adrenergic receptor stimulates γ-secretase activity and accelerates amyloid plaque formation. Nat. Med. 12, 1390–1396.10.1038/nm1485Suche in Google Scholar PubMed

Niimura, M., Isoo, N., Takasugi, N., Tsuruoka, M., Ui-Tei, K., Saigo, K., Morohashi, Y., Tomita, T., and Iwatsubo, T. (2005). Aph-1 contributes to the stabilization and trafficking of the γ-secretase complex through mechanisms involving intermolecular and intramolecular interactions. J. Biol. Chem. 280, 12967–12975.10.1074/jbc.M409829200Suche in Google Scholar PubMed

Offe, K., Dodson, S.E., Shoemaker, J.T., Fritz, J.J., Gearing, M., Levey, A.I., and Lah, J.J. (2006). The lipoprotein receptor LR11 regulates amyloid β production and amyloid precursor protein traffic in endosomal compartments. J. Neurosci. 26, 1596–1603.10.1523/JNEUROSCI.4946-05.2006Suche in Google Scholar PubMed PubMed Central

Park, H.J., Ran, Y., Jung, J.I., Holmes, O., Price, A.R., Smithson, L., Ceballos-Diaz, C., Han, C., Wolfe, M.S., Daaka, Y., et al. (2015). The stress response neuropeptide CRF increases amyloid-β production by regulating γ-secretase activity. EMBO J. 34, 1674–1686.10.15252/embj.201488795Suche in Google Scholar PubMed PubMed Central

Pasternak, S.H., Bagshaw, R.D., Guiral, M., Zhang, S., Ackerley, C.A., Pak, B.J., Callahan, J.W., and Mahuran, D.J. (2003). Presenilin-1, nicastrin, amyloid precursor protein, and γ-secretase activity are co-localized in the lysosomal membrane. J. Biol. Chem. 278, 26687–26694.10.1074/jbc.M304009200Suche in Google Scholar PubMed

Perez, R.G., Squazzo, S.L., and Koo, E.H. (1996). Enhanced release of amyloid β-protein from codon 670/671 “Swedish” mutant β-amyloid precursor protein occurs in both secretory and endocytic pathways. J. Biol. Chem. 271, 9100–9107.10.1074/jbc.271.15.9100Suche in Google Scholar PubMed

Pottier, C., Hannequin, D., Coutant, S., Rovelet-Lecrux, A., Wallon, D., Rousseau, S., Legallic, S., Paquet, C., Bombois, S., Pariente, J., et al. (2012). High frequency of potentially pathogenic SORL1 mutations in autosomal dominant early-onset Alzheimer disease. Mol. Psychiatry 17, 875–879.10.1038/mp.2012.15Suche in Google Scholar PubMed

Qi-Takahara, Y., Morishima-Kawashima, M., Tanimura, Y., Dolios, G., Hirotani, N., Horikoshi, Y., Kametani, F., Maeda, M., Saido, T.C., Wang, R., et al. (2005). Longer forms of amyloid β protein: implications for the mechanism of intramembrane cleavage by γ-secretase. J. Neurosci. 25, 436–445.10.1523/JNEUROSCI.1575-04.2005Suche in Google Scholar PubMed PubMed Central

Rajendran, L. and Annaert, W. (2012). Membrane trafficking pathways in Alzheimer’s disease. Traffic 13, 759–770.10.1111/j.1600-0854.2012.01332.xSuche in Google Scholar PubMed

Rechards, M., Xia, W., Oorschot, V.M., Selkoe, D.J., and Klumperman, J. (2003). Presenilin-1 exists in both pre- and post-Golgi compartments and recycles via COPI-coated membranes. Traffic 4, 553–565.10.1034/j.1600-0854.2003.t01-1-00114.xSuche in Google Scholar PubMed

Rogaeva, E., Meng, Y., Lee, J.H., Gu, Y., Kawarai, T., Zou, F., Katayama, T., Baldwin, C.T., Cheng, R., Hasegawa, H., et al. (2007). The neuronal sortilin-related receptor SORL1 is genetically associated with Alzheimer disease. Nat. Genet. 39, 168–177.10.1038/ng1943Suche in Google Scholar PubMed PubMed Central

Sannerud, R., Declerck, I., Peric, A., Raemaekers, T., Menendez, G., Zhou, L., Veerle, B., Coen, K., Munck, S., De Strooper, B., et al. (2011). ADP ribosylation factor 6 (ARF6) controls amyloid precursor protein (APP) processing by mediating the endosomal sorting of BACE1. Proc. Natl. Acad Sci. USA 108, E559–568.10.1073/pnas.1100745108Suche in Google Scholar PubMed PubMed Central

Sannerud, R., Esselens, C., Ejsmont, P., Mattera, R., Rochin, L., Tharkeshwar, A.K., De Baets, G., De Wever, V., Habets, R., Baert, V., et al. (2016). Restricted location of PSEN2/γ-secretase determines substrate specificity and generates an intracellular Aβ pool. Cell 166, 193–208.10.1016/j.cell.2016.05.020Suche in Google Scholar PubMed PubMed Central

Sato, C., Morohashi, Y., Tomita, T., and Iwatsubo, T. (2006). Structure of the catalytic pore of γ-secretase probed by the accessibility of substituted cysteines. J. Neurosci. 26, 12081–12088.10.1523/JNEUROSCI.3614-06.2006Suche in Google Scholar PubMed PubMed Central

Sato, T., Diehl, T.S., Narayanan, S., Funamoto, S., Ihara, Y., De Strooper, B., Steiner, H., Haass, C., and Wolfe, M.S. (2007). Active γ-secretase complexes contain only one of each component. J. Biol. Chem. 282, 33985–33993.10.1074/jbc.M705248200Suche in Google Scholar PubMed

Serneels, L., Van Biervliet, J., Craessaerts, K., Dejaegere, T., Horre, K., Van Houtvin, T., Esselmann, H., Paul, S., Schafer, M.K., Berezovska, O., et al. (2009). γ-Secretase heterogeneity in the Aph1 subunit: relevance for Alzheimer’s disease. Science 324, 639–642.10.1126/science.1171176Suche in Google Scholar PubMed PubMed Central

Seshadri, S., Fitzpatrick, A.L., Ikram, M.A., DeStefano, A.L., Gudnason, V., Boada, M., Bis, J.C., Smith, A.V., Carassquillo, M.M., Lambert, J.C., et al. (2010). Genome-wide analysis of genetic loci associated with Alzheimer disease. J. Am. Med. Assoc. 303, 1832–1840.10.1001/jama.2010.574Suche in Google Scholar PubMed PubMed Central

Shah, S., Lee, S.F., Tabuchi, K., Hao, Y.H., Yu, C., LaPlant, Q., Ball, H., Dann, C.E., 3rd, Sudhof, T., and Yu, G. (2005). Nicastrin functions as a γ-secretase-substrate receptor. Cell 122, 435–447.10.1016/j.cell.2005.05.022Suche in Google Scholar PubMed

Sisodia, S.S., Annaert, W., Kim, S.H., and De Strooper, B. (2001). Gamma-secretase: never more enigmatic. Trends Neurosci. 24, S2–6.10.1016/S0166-2236(00)01987-1Suche in Google Scholar PubMed

Spasic, D., Raemaekers, T., Dillen, K., Declerck, I., Baert, V., Serneels, L., Fullekrug, J., and Annaert, W. (2007). Rer1p competes with APH-1 for binding to nicastrin and regulates γ-secretase complex assembly in the early secretory pathway. J. Cell Biol. 176, 629–640.10.1083/jcb.200609180Suche in Google Scholar PubMed PubMed Central

Steiner, H., Romig, H., Pesold, B., Philipp, U., Baader, M., Citron, M., Loetscher, H., Jacobsen, H., and Haass, C. (1999). Amyloidogenic function of the Alzheimer’s disease-associated presenilin 1 in the absence of endoproteolysis. Biochemistry 38, 14600–14605.10.1021/bi9914210Suche in Google Scholar PubMed

Struhl, G. and Adachi, A. (2000). Requirements for presenilin-dependent cleavage of notch and other transmembrane proteins. Mol Cell 6, 625–636.10.1016/S1097-2765(00)00061-7Suche in Google Scholar

Sun, L., Li, X. and Shi, Y. (2016). Structural biology of intramembrane proteases: mechanistic insights from rhomboid and S2P to γ-secretase. Curr. Opin. Struct. Biol. 37, 97–107.10.1016/j.sbi.2015.12.008Suche in Google Scholar PubMed

Tagami, S., Okochi, M., Fukumori, A., Jiang, J., Yanagida, K., Nakayama, T., Morihara, T., Tanaka, T., Kudo, T., and Takeda, M. (2008). Processes of β-amyloid and intracellular cytoplasmic domain generation by presenilin/γ-secretase. Neurodegener Dis. 5, 160–162.10.1159/000113690Suche in Google Scholar PubMed

Takami, M., Nagashima, Y., Sano, Y., Ishihara, S., Morishima-Kawashima, M., Funamoto, S., and Ihara, Y. (2009). γ-Secretase: successive tripeptide and tetrapeptide release from the transmembrane domain of β-carboxyl terminal fragment. J. Neurosci. 29, 13042–13052.10.1523/JNEUROSCI.2362-09.2009Suche in Google Scholar PubMed PubMed Central

Takasugi, N., Tomita, T., Hayashi, I., Tsuruoka, M., Niimura, M., Takahashi, Y., Thinakaran, G., and Iwatsubo, T. (2003). The role of presenilin cofactors in the γ-secretase complex. Nature 422, 438–441.10.1038/nature01506Suche in Google Scholar PubMed

Takeo, K., Watanabe, N., Tomita, T., and Iwatsubo, T. (2012). Contribution of the γ-secretase subunits to the formation of catalytic pore of presenilin 1 protein. J. Biol. Chem. 287, 25834–25843.10.1074/jbc.M111.336347Suche in Google Scholar PubMed PubMed Central

Tebar, F., Bohlander, S.K., and Sorkin, A. (1999). Clathrin assembly lymphoid myeloid leukemia (CALM) protein: localization in endocytic-coated pits, interactions with clathrin, and the impact of overexpression on clathrin-mediated traffic. Mol. Biol. Cell. 10, 2687–2702.10.1091/mbc.10.8.2687Suche in Google Scholar PubMed PubMed Central

Thathiah, A. and De Strooper, B. (2011). The role of G protein-coupled receptors in the pathology of Alzheimer’s disease. Nat. Rev. Neurosci. 12, 73–87.10.1038/nrn2977Suche in Google Scholar PubMed

Thathiah, A., Spittaels, K., Hoffmann, M., Staes, M., Cohen, A., Horre, K., Vanbrabant, M., Coun, F., Baekelandt, V., Delacourte, A., et al. (2009). The orphan G protein-coupled receptor 3 modulates amyloid-β peptide generation in neurons. Science 323, 946–951.10.1126/science.1160649Suche in Google Scholar PubMed

Thathiah, A., Horre, K., Snellinx, A., Vandewyer, E., Huang, Y., Ciesielska, M., De Kloe, G., Munck, S., and De Strooper, B. (2013). β-arrestin 2 regulates Aβ generation and γ-secretase activity in Alzheimer’s disease. Nat. Med. 19, 43–49.10.1038/nm.3023Suche in Google Scholar PubMed

Tomita, T. (2014). Molecular mechanism of intramembrane proteolysis by γ-secretase. J. Biochem. 156, 195–201.10.1093/jb/mvu049Suche in Google Scholar PubMed

Tomita, T. and Iwatsubo, T. (2013). Structural biology of presenilins and signal peptide peptidases. J. Biol. Chem. 288, 14673–14680.10.1074/jbc.R113.463281Suche in Google Scholar PubMed PubMed Central

Urano, Y., Hayashi, I., Isoo, N., Reid, P.C., Shibasaki, Y., Noguchi, N., Tomita, T., Iwatsubo, T., Hamakubo, T., and Kodama, T. (2005). Association of active γ-secretase complex with lipid rafts. J. Lipid Res. 46, 904–912.10.1194/jlr.M400333-JLR200Suche in Google Scholar PubMed

Vaccari, T., Lu, H., Kanwar, R., Fortini, M.E., and Bilder, D. (2008). Endosomal entry regulates Notch receptor activation in Drosophila melanogaster. J. Cell Biol. 180, 755–762.10.1083/jcb.200708127Suche in Google Scholar PubMed PubMed Central

Vardarajan, B.N., Zhang, Y., Lee, J.H., Cheng, R., Bohm, C., Ghani, M., Reitz, C., Reyes-Dumeyer, D., Shen, Y., Rogaeva, E., et al. (2015). Coding mutations in SORL1 and Alzheimer disease. Ann. Neurol. 77, 215–227.10.1002/ana.24305Suche in Google Scholar PubMed PubMed Central

Vassar, R., Kuhn, P.H., Haass, C., Kennedy, M.E., Rajendran, L., Wong, P.C., and Lichtenthaler, S.F. (2014). Function, therapeutic potential and cell biology of BACE proteases: current status and future prospects. J. Neurochem. 130, 4–28.10.1111/jnc.12715Suche in Google Scholar PubMed PubMed Central

Vetrivel, K.S., Cheng, H., Lin, W., Sakurai, T., Li, T., Nukina, N., Wong, P.C., Xu, H., and Thinakaran, G. (2004). Association of γ-secretase with lipid rafts in post-Golgi and endosome membranes. J. Biol. Chem. 279, 44945–44954.10.1074/jbc.M407986200Suche in Google Scholar PubMed PubMed Central

von Kleist, L., Stahlschmidt, W., Bulut, H., Gromova, K., Puchkov, D., Robertson, M.J., MacGregor, K.A., Tomilin, N., Pechstein, A., Chau, N., et al. (2011). Role of the clathrin terminal domain in regulating coated pit dynamics revealed by small molecule inhibition. Cell 146, 471–484.10.1016/j.cell.2011.06.025Suche in Google Scholar PubMed

Wada, S., Morishima-Kawashima, M., Qi, Y., Misono, H., Shimada, Y., Ohno-Iwashita, Y., and Ihara, Y. (2003). Gamma-secretase activity is present in rafts but is not cholesterol-dependent. Biochemistry 42, 13977–13986.10.1021/bi034904jSuche in Google Scholar PubMed

Wakabayashi, T., Craessaerts, K., Bammens, L., Bentahir, M., Borgions, F., Herdewijn, P., Staes, A., Timmerman, E., Vandekerckhove, J., Rubinstein, E., et al. (2009). Analysis of the γ-secretase interactome and validation of its association with tetraspanin-enriched microdomains. Nat. Cell. Biol. 11, 1340–1346.10.1038/ncb1978Suche in Google Scholar PubMed

Watanabe, N., Tomita, T., Sato, C., Kitamura, T., Morohashi, Y., and Iwatsubo, T. (2005). Pen-2 is incorporated into the γ-secretase complex through binding to transmembrane domain 4 of presenilin 1. J. Biol. Chem. 280, 41967–41975.10.1074/jbc.M509066200Suche in Google Scholar PubMed

Willnow, T.E. and Andersen, O.M. (2013). Sorting receptor SORLA – a trafficking path to avoid Alzheimer disease. J. Cell Sci. 126, 2751–2760.10.1242/jcs.125393Suche in Google Scholar PubMed

Wolfe, M.S., Xia, W., Ostaszewski, B.L., Diehl, T.S., Kimberly, W.T., and Selkoe, D.J. (1999). Two transmembrane aspartates in presenilin-1 required for presenilin endoproteolysis and γ-secretase activity. Nature 398, 513–517.10.1038/19077Suche in Google Scholar PubMed

Yamakawa, H., Yagishita, S., Futai, E., and Ishiura, S. (2010). β-Secretase inhibitor potency is decreased by aberrant β-cleavage location of the “Swedish mutant” amyloid precursor protein. J. Biol. Chem. 285, 1634–1642.10.1074/jbc.M109.066753Suche in Google Scholar PubMed PubMed Central

Yan, R. and Vassar, R. (2014). Targeting the β secretase BACE1 for Alzheimer’s disease therapy. Lancet Neurol. 13, 319–329.10.1016/S1474-4422(13)70276-XSuche in Google Scholar PubMed PubMed Central

Yu, C., Kim, S.H., Ikeuchi, T., Xu, H., Gasparini, L., Wang, R., and Sisodia, S.S. (2001). Characterization of a presenilin-mediated amyloid precursor protein carboxyl-terminal fragment γ. Evidence for distinct mechanisms involved in γ-secretase processing of the APP and Notch1 transmembrane domains. J. Biol. Chem. 276, 43756–43760.10.1074/jbc.C100410200Suche in Google Scholar PubMed

Received: 2016-2-29
Accepted: 2016-7-4
Published Online: 2016-7-7
Published in Print: 2016-9-1

©2016 Walter de Gruyter GmbH, Berlin/Boston

Artikel in diesem Heft

  1. Frontmatter
  2. Guest Editorial
  3. Highlight: proteolytic networks across cellular boundaries
  4. HIGHLIGHT: IPS 2015 – 9TH GENERAL MEETING OF THE INTERNATIONAL PROTEOLYSIS SOCIETY
  5. A personal journey with matrix metalloproteinases
  6. Type II transmembrane serine proteases as potential targets for cancer therapy
  7. Membrane trafficking and proteolytic activity of γ-secretase in Alzheimer’s disease
  8. Dipeptidyl peptidase 9 substrates and their discovery: current progress and the application of mass spectrometry-based approaches
  9. Tetraspanin 8 is an interactor of the metalloprotease meprin β within tetraspanin-enriched microdomains
  10. Procathepsin E is highly abundant but minimally active in pancreatic ductal adenocarcinoma tumors
  11. Granzyme B inhibits keratinocyte migration by disrupting epidermal growth factor receptor (EGFR)-mediated signaling
  12. Myeloid conditional deletion and transgenic models reveal a threshold for the neutrophil survival factor Serpinb1
  13. Probing catalytic rate enhancement during intramembrane proteolysis
  14. Human 20S proteasome activity towards fluorogenic peptides of various chain lengths
  15. Research Articles/Short Communications
  16. Protein Structure and Function
  17. Biophysical analysis of three novel profilin-1 variants associated with amyotrophic lateral sclerosis indicates a correlation between their aggregation propensity and the structural features of their globular state
  18. The potential of the Galleria mellonella innate immune system is maximized by the co-presentation of diverse antimicrobial peptides
Heruntergeladen am 16.11.2025 von https://www.degruyterbrill.com/document/doi/10.1515/hsz-2016-0146/html?lang=de
Button zum nach oben scrollen