Molecular mechanism of the intramembrane cleavage of the β-carboxyl terminal fragment of amyloid precursor protein by γ-Secretase

Frontiers in Physiology

Volumn 5, Issue Nov, 2014, Pages

  Morishima Kawashima, Maho ^a  

^a HOKKAIDO UNIVERSITY   (Japan)

Author keywords

Alzheimer's disease; Amyloid precursor protein; Amyloid protein; Intramembrane proteolysis; Secretase

Indexed keywords

AMYLOID BETA PROTEIN[1-40]; AMYLOID BETA PROTEIN[1-42]; AMYLOID PRECURSOR PROTEIN; GAMMA SECRETASE; TRIPEPTIDE;

ALPHA HELIX; ALZHEIMER DISEASE; AMINO ACID SUBSTITUTION; AMINO TERMINAL SEQUENCE; ARTICLE; BETA CARBOXYL TERMINAL FRAGMENT; CARBOXY TERMINAL SEQUENCE; ENZYME ACTIVITY; HUMAN; MOLECULAR DYNAMICS; NONHUMAN; PROTEIN BINDING; PROTEIN CLEAVAGE; PROTEIN DEGRADATION; PROTEIN EXPRESSION; PROTEIN PROTEIN INTERACTION; PROTEIN SECRETION; PROTEIN STRUCTURE; SIGNAL TRANSDUCTION;

EID: 84912005649     PISSN: None     EISSN: 1664042X     Source Type: Journal    
DOI: 10.3389/fphys.2014.00463     Document Type: Article

References (55)

1. De Strooper, B., and Annaert, W. (2010). Novel research horizons for presenilins and γ-secretases in cell biology and disease. Annu. Rev. Cell Dev. Biol. 26, 235-260.
2. 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. doi: 10.1101/cshperspect.a006304.
3. Dimitrov, M., Alattia, J. R., Lemmin, T., Lehal, R., Fligier, A., Houacine, J., Hussain, I., Radtke, F., Dal Peraro, M., Beher, D., and Fraering, P. C. (2013). Alzheimer's disease mutations in APP but not γ -secretase modulators affect ε -cleavage-dependent AICD production. Nat. Commun. 4, 2246.
4. Extance, A. (2010). Alzheimer's failure raises questions about disease-modifying strategies. Nat. Rev. Drug Discov. 9, 749-751.
5. Fernandez, M. A., Klutkowski, J. A., Freret, T., and Wolfe, M. S. (2014). Alzheimer presenilin-1 mutations dramatically reduce trimming of long amyloid β-peptides (Aβ) by γ-secretase to increase 42-to-40 residue Aβ. J. Biol. Chem. pii: jbc. M114.581165. [Epub ahead of print]
6. Fluhrer, R., Grammer, G., Israel, L., Condron, M. M., Haffner, C., Friedmann, E., Böhland, C., Imhof, A., Martoglio, B., Teplow, D. B., and Haass, C. (2006). A γ-secretase-like intramembrane cleavage of TNFα by the GxGD aspartyl protease SPPL2b. Nat. Cell Biol. 8, 894-896.
7. Fukumori, A., Fluhrer, R., Steiner, H., and Haass, C. (2010). Three-amino acid spacing of presenilin endoproteolysis suggests a general stepwise cleavage of γ-secretase-mediated intramembrane proteolysis. J. Neurosci. 30, 7853-7862.
8. Funamoto, S., Morishima-Kawashima, M., Tanimura, Y., Hirotani, N., Saido, T. C., and Ihara, Y. (2004). Truncated carboxyl-terminal fragments of β-amyloid precursor protein are processed to amyloid β-proteins 40 and 42. Biochemistry. 43, 13532-13540.
9. 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. Hata, S., Fujishige, S., Araki, Y., Kato, N., Araseki, M., Nishimura, M., Hartmann, D., Saftig, P., Fahrenholz, F., Taniguchi, M., Urakami, K., Akatsu, H., Martins, R. N., Yamamoto, K., Maeda, M., Yamamoto, T., Nakaya, T., Gandy, S., and Suzuki, T. (2009). Alcadein cleavages by amyloid β-precursor protein (APP) α- and γ-secretases generate small peptides, p3-Alcs, indicating Alzheimer disease-related γ-secretase dysfunction. J. Biol. Chem. 284, 36024-36033.
11. Hu, J., Xue, Y., Lee, S., and Ha, Y. (2011). The crystal structure of GXGD membrane protease FlaK. Nature. 475, 528-531.
12. Hur, J. Y., Welander, H., Behbahani, H., Aoki, M., Frånberg, J., Winblad, B., Frykman, S., and Tjernberg, L. O. (2008). Active γ-secretase is localized to detergent-resistant membranes in human brain. FEBS J. 275, 1174-1187.
13. 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.
14. Kakuda, N., Funamoto, S., Yagishita, S., Takami, M., Osawa, S., Dohmae, N., and Ihara, Y. (2006). Equimolar production of amyloid β-protein and amyloid precursor protein intracellular domain from β-carboxyl-terminal fragment by γ-secretase. J. Biol. Chem. 281, 14776-14786.
15. Kopan, R., and Ilagan, M. X. (2004). γ-Secretase: proteasome of the membrane? Nat. Rev. Mol. Cell Biol. 5, 499-504.
16. Kuperstein, I., Broersen, K., Benilova, I., Rozenski, J,. Jonckheere, W., Debulpaep, M., Vandersteen, A., Segers-Nolten, I., Van Der Werf, K., Subramaniam, V., Braeken, D., Callewaert, G., Bartic, C., D'Hooge, R., Martins, I. C., Rousseau, F., Schymkowitz, J., and De Strooper, B. (2010). Neurotoxicity of Alzheimer's disease Aβ peptides is induced by small changes in the Aβ42 to Aβ40 ratio. EMBO J. 29, 3408-3420.
17. Lammich, S., Okochi, M., Takeda, M., Kaether, C., Capell, A., Zimmer, A. K., Edbauer, D., Walter, J., Steiner, H., and Haass, C. (2002). Presenilin-dependent intramembrane proteolysis of CD44 leads to the liberation of its intracellular domain and the secretion of an Aβ-like peptide. J. Biol. Chem. 277, 44754-44759.
18. Lemmin, T., Dimitrov, M., Fraering, P. C., and Dal Peraro, M. (2014). Perturbations of the straight transmembrane α-helical structure of the amyloid precursor protein affect its processing by γ-secretase. J. Biol. Chem. 289, 6763-6774.
19. Li, X., Dang, S., Yan, C., Gong, X., Wang, J., and Shi, Y. (2013). Structure of a presenilin family intramembrane aspartate protease. Nature. 493, 56-61.
20. Lichtenthaler, S. F., Wang, R., Grimm, H., Uljon, S. N., Masters, C. L., and Beyreuther, K. (1999). Mechanism of the cleavage specificity of Alzheimer's disease γ-secretase identified by phenylalanine-scanning mutagenesis of the transmembrane domain of the amyloid precursor protein. Proc. Natl. Acad. Sci. U. S. A. 96, 3053-3058.
21. Lu, P., Bai, X. C., Ma, D., Xie, T., Yan, C., Sun, L., Yang, G., Zhao, Y., Zhou, R., Scheres, S. H., and Shi, Y. (2014). Three-dimensional structure of human γ-secretase. Nature. 512, 166-170.
22. Lu, W. M., and Tycko, R. (2011). Evidence from solid-state NMR for nonhelical conformations in the transmembrane domain of the amyloid precursor protein. Biophys. J. 100, 711-719.
23. Matsumura, N., Takami, M., Okochi, M., Wada-Kakuda, S., Fujiwara, H., Tagami, S., Funamoto, S., Ihara, Y., and Morishima-Kawashima, M. (2014). γ-Secretase associated with lipid rafts: multiple interactive pathways in the stepwise processing of β-carboxyl-terminal fragment. J Biol Chem. 289, 5109-5121.
24. Munter, L. M., Voigt, P., Harmeier, A., Kaden, D., Gottschalk, K. E., Weise, C., Pipkorn, R., Schaefer, M., Langosch, D., and Multhaup, G. (2007). GxxxG motifs within the amyloid precursor protein transmembrane sequence are critical for the etiology of Aβ42. EMBO J. 26, 1702-1712.
25. Okamoto, I., Kawano, Y., Murakami, D., Sasayama, T., Araki, N., Miki, T., Wong, A. J., and Saya, H. (2001). Proteolytic release of CD44 intracellular domain and its role in the CD44 signaling pathway. J. Cell Biol. 155, 755-762.
26. Okochi, M., Steiner, H., Fukumori, A., Tanii, H., Tomita, T., Tanaka, T., Iwatsubo, T., Kudo, T., Takeda, M., and Haass, C. (2002). Presenilins mediate a dual intramembranous γ-secretase cleavage of Notch-1. EMBO J. 21, 5408-5416.
27. Okochi, M., Tagami, S., Yanagida, K., Takami, M., Kodama, T. S., Mori, K., Nakayama, T., Ihara, Y., and Takeda, M. (2013). γ-Secretase modulators and presenilin 1 mutants act differently on presenilin/γ-secretase function to cleave Aβ42 and Aβ43. Cell Rep. 3, 42-51.
28. Olsson, F., Schmidt, S., Althoff, V., Munter, L. M., Jin, S., Rosqvist, S., Lendahl, U., Multhaup, G., and Lundkvist, J. (2014). Characterization of intermediate steps in amyloid β (Aβ) production under near-native conditions. J. Biol. Chem. 289, 1540-1550.
29. Osenkowski, P., Ye, W., Wang, R., Wolfe, M. S., and Selkoe, D. J. (2008). Direct and potent regulation of γ-secretase by its lipid microenvironment. J. Biol. Chem. 283, 22529-22540.
30. Pester, O., Barrett, P. J., Hornburg, D., Hornburg, P., Pröbstle, R., Widmaier, S., Kutzner, C., Dürrbaum, M., Kapurniotu, A., Sanders, C. R., Scharnagl, C., and Langosch, D. (2013). The backbone dynamics of the amyloid precursor protein transmembrane helix provides a rationale for the sequential cleavage mechanism of γ-secretase. J. Am. Chem. Soc. 135, 1317-1329.
31. Piao, Y., Kimura, A., Urano, S., Saito, Y., Taru, H., Yamamoto, T., Hata, S., and Suzuki, T. (2013). Mechanism of intramembrane cleavage of alcadeins by γ-secretase. PLoS One. 8, e62431. doi: 10.1371/journal.pone.0062431.
32. Qi-Takahara, Y., Morishima-Kawashima, M., Tanimura, Y., Dolios, G., Hirotani, N., Horikoshi, Y., Kametani, F., Maeda, M., Saido, T. C., Wang, R., and Ihara, Y. (2005). Longer forms of amyloid β protein: implications for the mechanism of intramembrane cleavage by γ-secretase. J. Neurosci. 25, 436-445.
33. Quintero-Monzon, O., Martin, M. M., Fernandez, M. A., Cappello, C. A., Krzysiak, A. J., Osenkowski, P., and Wolfe, M.S. (2011). Dissociation between the processivity and total activity of γ-secretase: implications for the mechanism of Alzheimer's disease-causing presenilin mutations. Biochemistry. 50, 9023-9035.
34. Sastre, M., Steiner, H,. Fuchs, K., Capell, A., Multhaup, G., Condron, M. M., Teplow, D. B., and Haass, C. (2001). Presenilin-dependent γ-secretase processing of β-amyloid precursor protein at a site corresponding to the S3 cleavage of Notch. EMBO Rep. 2, 835-841.
35. Saito, T., Suemoto, T., Brouwers, N., Sleegers, K., Funamoto, S., Mihira, N., Matsuba, Y., Yamada, K., Nilsson, P., Takano, J., Nishimura, M., Iwata, N., Van Broeckhoven, C., Ihara, Y., and Saido, T. C. (2011). Potent amyloidogenicity and pathogenicity of Aβ43. Nat. Neurosci. 14, 1023-1032.
36. 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.
37. Sato, T., Dohmae, N., Qi, Y., Kakuda, N., Misonou, H., Mitsumori, R., Maruyama, H., Koo, E. H., Haass, C., Takio, K., Morishima-Kawashima, M., Ishiura, S., and Ihara, Y. (2003). Potential link between amyloid β-protein 42 and C-terminal fragment γ49-99 of β-amyloid precursor protein. J. Biol. Chem. 278, 24294-24301.
38. Sato, T., Tang, T. C., Reubins, G., Fei, J. Z., Fujimoto, T., Kienlen-Campard, P., Constantinescu, S. N., Octave, J. N., Aimoto, S., and Smith, S. O. (2009). A helix-to-coil transition at the ε-cut site in the transmembrane dimer of the amyloid precursor protein is required for proteolysis. Proc. Natl. Acad. Sci. U. S. A. 106, 1421-1426.
39. Sato, T., Tanimura, Y., Hirotani, N., Saido, T. C., Morishima-Kawashima, M., and Ihara, Y. (2005). Blocking the cleavage at midportion between γ- and ε-sites remarkably suppresses the generation of amyloid β-protein. FEBS Lett. 579, 2907-2912.
40. Schroeter, E. H., Kisslinger, J. A., and Kopan, R. (1998). Notch-1 signalling requires ligand-induced proteolytic release of intracellular domain. Nature. 393, 382-386.
41. Selkoe, D. J. (2011). Alzheimer's disease. Cold Spring Harb. Perspect Biol. 3, pii: a004457. doi: 10.1101/cshperspect.a004457.
42. Shah, S., Lee, S. F., Tabuchi, K., Hao, Y. H., Yu, C., LaPlant, Q., Ball, H., Dann, C. E., 3rd, Südhof, T., and Yu, G. (2005). Nicastrin functions as a γ-secretase-substrate receptor. Cell. 122, 435-447.
43. Shimojo, M., Sahara, N., Mizoroki, T., Funamoto, S., Morishima-Kawashima, M., Kudo, T., Takeda, M., Ihara, Y., Ichinose, H., and Takashima, A. (2008). Enzymatic characteristics of I213T mutant presenilin-1/γ-secretase in cell models and knock-in mouse brains: familial Alzheimer disease-linked mutation impairs γ-site cleavage of amyloid precursor protein C-terminal fragment β. J. Biol. Chem. 283, 16488-16496.
44. 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.
45. Tagami, S., Okochi, M., Yanagida, K., Ikuta, A., Fukumori, A., Matsumoto, N., Ishizuka-Katsura, Y., Nakayama, T., Itoh, N., Jiang, J., Nishitomi, K., Kamino, K., Morihara, T., Hashimoto, R., Tanaka, T., Kud, T., Chiba, S., and Takeda, M. (2008). Regulation of Notch signaling by dynamic changes in the precision of S3 cleavage of Notch-1. Mol. Cell Biol. 28, 165-176.
46. Tolia, A., Chavez-Gutierrez, L., and De Strooper, B. (2006). Contribution of presenilin TMDs 6 and 7 to a water-containing cavity in the γ-secretase complex. J. Biol. Chem. 281, 27633-27642.
47. 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.
48. Vetrivel, K. S., and Thinakaran, G. (2010). Membrane rafts in Alzheimer's disease β-amyloid production. Biochim. Biophys. Acta. 1801, 860-867.
49. Wada, S., Morishima-Kawashima, M., Qi, Y., Misono, H., Shimada, Y., Ohno-Iwashita, Y., and Ihara, Y. (2003). γ-Secretase activity is present in rafts but is not cholesterol-dependent. Biochemistry. 42, 13977-13986.
50. Weidemann, A., Eggert, S., Reinhard, F. B., Vogel, M., Paliga, K., Baier, G., Masters, C. L., Beyreuther, K., and Evin, G. (2002). A novel ε-cleavage within the transmembrane domain of the Alzheimer amyloid precursor protein demonstrates homology with Notch processing. Biochemistry. 41, 2825-2835.
51. 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 γss-secretase activity. Nature. 398, 513-517.
52. Yagishita, S., Morishima-Kawashima, M., Ishiura, S., and Ihara, Y. (2008). Aβ46 is processed to Aβ40 and Aβ43, but not to Aβ42, in the low density membrane domains. J. Biol. Chem. 283, 733-738.
53. Yagishita, S., Morishima-Kawashima, M., Tanimura, Y., Ishiura, S., and Ihara, Y. (2006). DAPT-induced intracellular accumulations of longer amyloid β-proteins: further implications for the mechanism of intramembrane cleavage by γ-secretase. Biochemistry. 45, 3952-3960.
54. Yanagida, K., Okochi, M., Tagami, S., Nakayama, T., Kodama, T. S., Nishitomi, K., Jiang, J., Mori, K., Tatsumi, S., Arai, T., Ikeuchi, T., Kasuga, K., Tokuda, T., Kondo, M., Ikeda, M., Deguchi, K., Kazu, H., Tanaka, T., Morihara, T., Hashimoto, R., Kudo, T., Steiner, H., Haass, C., Tsuchiya, K., Akiyama, H., Kuwano, R., and Takeda, M. (2009). The 28-amino acid form of an APLP1-derived Aβ-like peptide is a surrogate marker for Aβ42 production in the central nervous system. EMBO Mol. Med. 1, 223-235.
55. Zhao, G., Mao, G., Tan, J., Dong, Y., Cui, M. Z., Kim, S. H., and Xu, X. (2004). Identification of a new presenilin-dependent ζ-cleavage site within the transmembrane domain of amyloid precursor protein. J. Biol. Chem. 279, 50647-50650.