Intramembrane proteolysis by presenilin and presenilin-like proteases

Journal of Cell Science

Volumn 116, Issue 14, 2003, Pages 2839-2844

  Xia, Weiming ^a   Wolfe, Michael S ^a  

^a HARVARD MEDICAL SCHOOL   (United States)

Author keywords

Alzheimer's disease; Amyloid; Presenilin; Secretase; Signal peptide peptidase

Indexed keywords

AMYLOID PRECURSOR PROTEIN; ASPARTIC PROTEINASE; GAMMA SECRETASE; MEMBRANE PROTEIN; NICASTRIN; NOTCH RECEPTOR; PEPTIDASE; PRESENILIN 1; PRESENILIN 2; PROTEINASE; RECEPTOR PROTEIN; SIGNAL PEPTIDE;

AFFINITY LABELING; ALZHEIMER DISEASE; CELL DIFFERENTIATION; CELL MATURATION; ENZYME ANALYSIS; EUKARYOTE; HUMAN; HYDROPHOBICITY; MEMBRANE RECONSTITUTION; MUTAGENESIS; NONHUMAN; PRIORITY JOURNAL; PROTEIN DEGRADATION; PROTEIN DOMAIN; PROTEIN HYDROLYSIS; PROTEIN ISOLATION; PROTEIN MOTIF; REGULATORY MECHANISM; REVIEW; SIGNAL TRANSDUCTION;

ALZHEIMER DISEASE; AMINO ACID MOTIFS; AMYLOID PRECURSOR PROTEIN SECRETASES; ANIMALS; ASPARTIC ENDOPEPTIDASES; BINDING SITES; CAENORHABDITIS ELEGANS; CAENORHABDITIS ELEGANS PROTEINS; CELL DIFFERENTIATION; CELL MEMBRANE; ENDOPEPTIDASES; HOMEODOMAIN PROTEINS; MEMBRANE PROTEINS; MICE; MODELS, BIOLOGICAL; MUTAGENESIS; MUTATION; PROTEIN CONFORMATION; PROTEIN STRUCTURE, TERTIARY; PROTEINS; RECEPTORS, NOTCH; SIGNAL TRANSDUCTION;

EUKARYOTA;

EID: 0042671326     PISSN: 00219533     EISSN: None     Source Type: Journal    
DOI: 10.1242/jcs.00651     Document Type: Review

References (71)

1. Arawaka, S., Hasegawa, H., Tandon, A., Janus, C., Chen, F., Yu, G., Kikuchi, K., Koyama, S., Kato, T., Fraser, P. E. and St George-Hyslop, P. (2002). The levels of mature glycosylated nicastrin are regulated and correlate with gamma-secretase processing of amyloid beta-precursor protein. J. Neurochem. 83, 1065-1071.
2. Beynon, R. and Salvesen, G. (2001). Commercially available proteinase inhibitors. In Proteolytic Enzymes: A Practical Approach (ed. R. Beynon and J. Bond), pp. 317-330. Oxford University Press, New York.
3. Borchelt, D. R., Thinakaran, G., Eckman, C. B., Lee, M. K., Davenport, F., Ratovitsky, T., Prada, C.-M., Kim, G., Seekins, S., Yager, D. et al. (1996). Familial Alzheimer's disease-linked presenilin 1 variants elevate Aβ1-42/1-40 ratio in vitro and in vivo. Neuron 17, 1005-1013.
4. Capell, A., Grunberg, J., Pesold, B., Diehlmann, A., Citron, M., Nixon, R., Beyreuther, K., Selkoe, D. J. and Haass, C. (1998). The proteolytic fragments of the Alzheimer's disease-associated presenilin-1 form heterodimers and occur as a 100-150-kDa molecular mass complex. J. Biol. Chem. 273, 3205-3211.
5. Citron, M., Westaway, D., Xia, W., Carlson, G., Diehl, T., Levesque, G., Johnson-Wood, K., Lee, M., Seubert, P., Davis, A. et al. (1997). Mutant presenilins of Alzheimer's disease increase production of 42-residue amyloid β-protein in both transfected cells and transgenic mice. Nat. Med. 3, 67-72.
6. Davis, J. A., Naruse, S., Chen, H., Eckman, C., Younkin, S., Price, D. L., Borchelt, D. R., Sisodia, S. S. and Wong, P. C. (1998). An Alzheimer's disease-linked PS1 variant rescues the developmental abnormalities of PS1-deficient embryos. Neuron 20, 603-609.
7. De Strooper, B., Saftig, P., Craessaerts, K., Vanderstichele, H., Gundula, G., Annaert, W., von Figura, K. and van Leuven, F. (1998). Deficiency of presenilin-1 inhibits the normal cleavage of amyloid precursor protein. Nature 391, 387-390.
8. De Strooper, B., Annaert, W., Cupers, P., Saftig, P., Craessaerts, K., Mumm, J. S., Schroeter, E. H., Schrijvers, V., Wolfe, M. S., Ray, W. J., Goate, A. and Kopan, R. (1999). A presenilin-1-dependent gamma-secretase-like protease mediates release of Notch intracellular domain. Nature 398, 518-522.
9. Doan, A., Thinakaran, G., Borchelt, D. R., Slunt, H. H., Ratovitsky, T., Podlisny, M., Selkoe, D. J., Seeger, M., Gandy, S. E., Price, D. L. and Sisodia, S. S. (1996). Protein topology of presenilin 1. Neuron 17, 1023-1030.
10. Duff, K., Eckman, C., Zehr, C., Yu, X., Prada, C.-M., Perez-Tur, J., Hutton, M., Buee, L., Harigaya, Y., Yager, D. et al. (1996). Increased amyloid-β42(43) in brains of mice expressing mutant presenilin 1. Nature 383, 710-713.
11. Edbauer, D., Winkler, E., Haass, C. and Steiner, H. (2002). Presenilin and nicastrin regulate each other and determine amyloid b-peptide production via complex formation. Proc. Natl. Acad. Sci. USA 99, 8666-8671.
12. Edbauer, D., Winkler, E., Regula, J. T., Pesold, B., Steiner, H. and Haass, C. (2003). Reconstitution of gamma-secretase activity. Nat. Cell Biol. 5, 486-488.
13. 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, 428-454.
14. Esler, W. P., Kimberly, W., Ostaszewski, B., Ye, W., Diehl, T., Selkoe, D. and Wolfe, M. S. (2002). Activity dependent isolation of the presenilin-γ-secretase complex reveals nicastrin and a γ substrate. Proc. Natl. Acad. Sci. USA 99, 2720-2725.
15. Evin, G., Sharples, R., Weidemann, A., Reinhard, F., Carbone, V., Culvenor, J., Holsinger, R., Sernee, M., Beyreuther, K. and Masters, C. (2001). Aspartyl protease inhibitor pepstatin binds to the presenilins of Alzheimer's disease. Biochemistry 40, 8359-8368.
16. Fortini, M. E. (2002). Gamma-secretase-mediated proteolysis in cell-surface-receptor signalling. Nat. Rev. Mol. Cell Biol. 3, 673-684.
17. Francis, R., McGrath, G., Zhang, J., Ruddy, D., Sym, M., Apfeld, J., Nicoll, M., Maxwell, M., Hai, B., Ellis, M. C. et al. (2002). aph-1 and pen-2 are required for Notch pathway signaling, γ-secretase cleavage of bAPP and presenilin protein accumulation. Dev. Cell 3, 85-97.
18. Goutte, C., Tsunozaki, M., Hale, V. A. and Priess, J. R. (2002). APH-1 is a multipass membrane protein essential for the Notch signaling pathway in Caenorhabditis elegans embryos. Proc. Natl. Acad. Sci. USA 99, 775-779.
19. Gravina, S. A., Ho, L., Eckman, C. B., Long, K. E., Otvos, L. J., Younkin, L. H., Suzuki, N. and Younkin, S. G. (1995). Amyloid β protein (Aβ) in Alzheimer's disease brain. J. Biol. Chem. 270, 7013-7016.
20. Grigorenko, A. P., Moliaka, Y. K., Korovaitseva, G. I. and Rogaev, E. I. (2002). Novel class of polytopic proteins with domains associated with putative protease activity. Biochemistry (Mosc) 67, 826-835.
21. Gu, Y., Chen, F., Sanjo, N., Kawarai, T., Hasegawa, H., Duthie, M., Li, W., Ruan, X., Luthra, A., Mount, H. T. et al. (2003). APH-1 interacts with mature and immature forms of presenilins and nicastrin and may play a role in maturation of presenilin-nicastrin complexes. J. Biol. Chem. 278, 7374-7380.
22. Herreman, A., Serneels, L., Annaert, W., Collen, D., Schoonjans, L. and de Strooper, B. (2000). Total inactivation of gamma-secretase activity in presenilin-deficient embryonic stem cells. Nat. Cell Biol. 2, 461-462.
23. Herreman, A., van Gassen, G., Bentahir, M., Nyabi, O., Craessaerts, K., Mueller, U., Annaert, W. and 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.
24. Iwatsubo, T., Odaka, A., Suzuki, N., Mizusawa, H., Nukina, H. and Ihara, Y. (1994). Visualization of A beta 42(43) and A beta 40 in senile plaques with end-specific A beta monoclonals: evidence that an initially deposited species is A beta 42(43). Neuron 13, 45-53.
25. Kim, D., Ingano, L. and Kovacs, D. (2002). Nectin-1α, an immunoglobulin-like receptor involved in the formation of synapses, is a substrate for presenilin/γ-secretase-like cleavage. J. Biol. Chem. 277, 49976-49981.
26. Kimberly, W. T., Xia, W., Rahmati, R., Wolfe, M. S. and Selkoe, D. J. (2000). The transmembrane aspartates in presenilin 1 and 2 are obligatory for γ-secretase activity and amyloid β-protein generation. J. Biol. Chem. 275, 3173-3178.
27. Kimberly, W. T., LaVoie, M. J., Ostaszewski, B. L., Ye, W., Wolfe, M. S. and Selkoe, D. J. (2002). Complex N-linked glycosylated nicastrin associates with active gamma-secretase and undergoes tight cellular regulation. J. Biol. Chem. 277, 35113-35117.
28. Kimberly, W., LaVoie, M., Ostaszewski, B., Ye, W., Wolfe, M. and Selkoe, D. (2003). γ-Secretase is a membrane protein complex comprised of presenilin, nicastrin, aph-1 and pen-2. Proc. Natl. Acad. Sci. USA (in press).
29. Kopan, R. and Goate, A. (2002). Aph-2/Nicastrin: an essential component of gamma-secretase and regulator of Notch signaling and Presenilin localization. Neuron 33, 321-324.
30. 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 Abeta-like peptide. J. Biol. Chem. 277, 44754-44759.
31. LaPointe, C. F. and Taylor, R. K. (2000). The type 4 prepilin peptidases comprise a novel family of aspartic acid proteases. J. Biol. Chem. 275, 1502-1510.
32. Lee, H. J., Jung, K. M., Huang, Y. Z., Bennett, L. B., Lee, J. S., Mei, L. and Kim, T. W. (2002a). Presenilin-dependent gamma-secretase-like intramembrane cleavage of ErbB4. J Biol Chem. 277, 6318-6323.
33. Lee, S., Shah, S., Li, H., Yu, C., Han, W. and Yu, G. (2002b). Mammalian APH-1 interacts with presenilin and nicastrin, and is required for intramembrane proteolysis of APP and Notch. J. Biol. Chem. 277, 45013-45019.
34. Leem, J. Y., Vijayan, S., Han, P., Cai, D., Machura, M., Lopes, K. O., Veselits, M. L., Xu, H. and Thinakaran, G. (2002). Presenilin 1 is required for maturation and cell surface accumulation of nicastrin. J. Biol. Chem. 277, 19236-19240.
35. Lemberg, M. and Martoglio, B. (2002). Requirements for signal peptide peptidase-catalyzed intramembrane proteolysis. Mol. Cell 10, 735-744.
36. Lemere, C. A., Lopera, F., Kosik, K. S., Lendon, C. L., Ossa, J., Saido, T. C., Yamaguchi, H., Ruiz, A., Martinez, A., Madrigal, L. et al. (1996). The E280A presenilin 1 Alzheimer mutation produces increased Aβ42 deposition and severe cerebellar pathology. Nature Med. 2, 1146-1150.
37. Levy-Lahad, E., Wijsman, E. M., Nemens, E., Anderson, L., Goddard, A. B., Weber, J. L., Bird, T. D. and Schellenberg, G. D. (1995). A familial Alzheimer's disease locus on chromosome 1. Science 269, 970-973.
38. Li, X. and Greenwald, I. (1998). Additional evidence for an eight-transmembrane-domain topology for Caenorhabditis elegans and human presenilins. Proc. Natl. Acad. Sci. USA 95, 7109-7114.
39. Li, Y.-M., Xu, M., Lai, M.-T., Huang, Q., Castro, J. L., DiMuzio-Mower, J., Harrison, T., Lellis, C., Nadin, A., Neduvelli, J. G. et al. (2000). Photoactivated γ-secretase inhibitors directed to the active site covalently label presenilin 1. Nature 405, 689-694.
40. Luo, W. J., Wang, H., Li, H., Kim, B. S., Shah, S., Lee, H. J., Thinakaran, G., Kim, T. W., Yu, G. and Xu, H. (2003). PEN-2 and APH-1 coordinately regulate proteolytic processing of presenilin 1. J. Biol. Chem. 278, 7850-7854.
41. Mahon, P. and Bateman, A. (2000). The PA domain: a protease-associated domain. Protein Sci. 9, 1930-1934.
42. Mann, D. M. A., Iwatsubo, T., Cairns, N. J., Lantos, P. L., Nochlin, D., Sumi, S. M., Bird, T. D., Poorkaj, P., Hardy, J., Hutton, M. et al. (1996a). Amyloid beta protein (A-beta) deposition in chromosome 14-linked Alzheimer's disease - predominance of A-beta (42(43)). Ann. Neurol. 40, 149-156.
43. 42(43) in plaques in cases of Alzheimer's disease and hereditary cerebral hemorrhage associated with muations in the amyloid precursor protein gene. Am. J. Pathol. 148, 1257-1266.
44. Marambaud, P., Shioi, J., Serban, G., Georgakopoulos, A., Sarner, S., Nagy, V., Baki, L., Wen, P., Efthimiopoulos, S., Shao, Z., Wisniewski, T. and Robakis, N. K. (2002). A presenilin-1/gamma-secretase cleavage releases the E-cadherin intracellular domain and regulates disassembly of adherens junctions. EMBO J. 21, 1948-1956.
45. May, P., Reddy, Y. K. and Herz, J. (2002). Proteolytic processing of low density lipoprotein receptor-related protein mediates regulated release of its intracellular domain. J. Biol. Chem. 277, 18736-18743.
46. Ni, C. Y., Murphy, M. P., Golde, T. E. and Carpenter, G. (2001). gamma-Secretase cleavage and nuclear localization of ErbB-4 receptor tyrosine kinase. Science 294, 2179-2181.
47. 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 gamma-secretase cleavage of Notch-1. EMBO J. 21, 5408-5416.
48. Ponting, C. P., Hutton, M., Nyborg, A., Baker, M., Jansen, K. and Golde, T. E. (2002). Identification of a novel family of presenilin homologues. Hum. Mol. Genet. 11, 1037-1044.
49. Qian, S., Jiang, P., Guan, X. M., Singh, G., Trumbauer, M. E., Yu, H., Chen, H. Y., van de Ploeg, L. H. and Zheng, H. (1998). Mutant human presenilin 1 protects presenilin 1 null mouse against embryonic lethality and elevates Abeta1-42/43 expression. Neuron 20, 611-617.
50. Rogaev, E. I., Sherrington, R., Rogaeva, E. A., Levesque, G., Ikeda, M., Liang, Y., Chi, H., Lin, C., Holamn, K., Tsuda, T. et al. (1995). Familial Alzheimer's disease in kindreds with missense mutations in a gene on chromosome 1 related to the Alzheimer's disease type 3 gene. Nature 376, 775-778.
51. Scheuner, D., Eckman, C., Jensen, M., Song, X., Citron, M., Suzuki, N., Bird, T. D., Hardy, J., Hutton, M., Kukull, W. et al. (1996). Secreted amyloid β-protein similar to that in the senile plaques of Alzheimer's disease is increased in vivo by the presenilin 1 and 2 and APP mutations linked to familial Alzheimer's disease. Nat. Med. 2, 864-870.
52. Seiffert, D., Bradley, J. D., Rominger, C. M., Rominger, D. H., Yang, F., Meredith, J. E., Jr, Wang, Q., Roach, A. H., Thompson, L. A., Spitz, S. M. et al. (2000). Presenilin-1 and -2 are molecular targets for gamma-secretase inhibitors. J. Biol. Chem. 275, 34086-34091.
53. Shearman, M. S., Beher, D., Clarke, E. E., Lewis, H. D., Harrison, T., Hunt, P., Nadin, A., Smith, A. L., Stevenson, G. and Castro, J. L. (2000). L-685,458, an aspartyl protease transition state mimic, is a potent inhibitor of amyloid beta-protein precursor gamma-secretase activity. Biochemistry 39, 8698-8704.
54. Shen, J., Bronson, R. T., Chen, D. F., Xia, W., Selkoe, D. J. and Tonegawa, S. (1997). Skeletal and CNS defects in presnilin-1 deficient mice. Cell 89, 629-639.
55. Sherrington, R., Rogaev, E. I., Liang, Y., Rogaeva, E. A., Levesque, G., Ikeda, M., Chi, H., Lin, C., Li, G., Holman, K. et al. (1995). Cloning of a novel gene bearing missense mutations in early onset familial Alzheimer disease. Nature 375, 754-760.
56. Steiner, H., Duff, K., Capell, A., Romig, H., Grim, M. G., Lincoln, S., Hardy, J., Yu, X., Picciano, M., Fechteler, K. et al. (1999). A loss of function mutation of presenilin-2 interferes with amyloid β-peptide production and Notch signaling. J. Biol. Chem. 274, 28669-28673.
57. Steiner, H., Kostka, M., Romig, H., Basset, G., Pesold, B., Hardy, J., Capell, A., Meyn, L., Grim, M. L., Baumeister, R. et al. (2000). Glycine 384 is required for presenilin-1 function and is conserved in bacterial polytopic aspartyl proteases. Nat. Cell Biol. 2, 848-851.
58. Steiner, H., Winkler, E., Edbauer, D., Prokop, S., Basset, G., Yamasaki, A., Kostka, M. and Haass, C. (2002). PEN-2 is an integral component of the gamma -secretase complex required for coordinated expression of presenilin and nicastrin. J. Biol. Chem. 277, 39062-39065.
59. 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 gamma-secretase complex. Nature 422, 438-441.
60. Thinakaran, G., Borchelt, D. R., Lee, M. K., Slunt, H. H., Spitzer, L., Kim, G., Rotovitsky, T., Davenport, F., Nordstedt, C., Seeger, M. et al. (1996). Endoprotreolysis of presenilin 1 and accumulation of processed derivatives in vivo. Neuron 17, 181-190.
61. Tomita, T., Watabiki, T., Takikawa, R., Morohashi, Y., Takasugi, N., Kopan, R., de Strooper, B. and Iwatsubo, T. (2001). The first proline of PALP motif at the C terminus of presenilins is obligatory for stabilization,complex formation and γ-secretase activities of presenilins. J. Biol. Chem. 276, 33273-33281.
62. Tomita, T., Katayama, R., Takikawa, R. and Iwatsubo, T. (2002). Complex N-glycosylated form of nicastrin is stabilized and selectively bound to presenilin fragments. FEBS Lett. 520, 117-121.
63. Weihofen, A., Binns, K., Lemberg, M. K., Ashman, K. and Martoglio, B. (2002). Identification of signal peptide peptidase, a presenilin-type aspartic protease. Science 296, 2215-2218.
64. Wolfe, M. S., Xia, W., Moore, C. L., Leatherwood, D. D., Ostaszewski, B. L., Rahmati, T., Donkor, I. O. and Selkoe, D. J. (1999a). Peptidomimetic probes and molecular modeling suggest Alzheimer's γ-secretase is an intramembrane-cleaving aspartyl protease. Biochemistry 38, 4720-4727.
65. Wolfe, M. S., Xia, W., Ostaszewski, B. L., Diehl, T. S., Kimberly, W. T. and Selkoe, D. J. (1999b). Two transmembrane aspartates in presenilin-1 required for presenilin endoproteolysis and γ-secretase activity. Nature 398, 513-517.
66. Wong, P., Zhen, H., Chen, H., Becher, M. W., Sirinathsinghji, D. J., Trumbauer, M. E., Proce, D. L., van der Ploeg, L. H. T. and Sisodia, S. S. (1997). Presenilin 1 is required for Notch 1 and D111 expression in the paraxial mesoderm. Nature 397, 288-292.
67. Xia, W., Zhang, J., Kholodenko, D., Citron, M, Podlisny, M. B., Teplow, D. B., Haass, C., Seubert, P., Koo, E. H. and Selkoe, D. J. (1997). Enhanced production and oligomerization of the 42-residue amyloid β-protein by Chinese hamster ovary cells stably expressing mutant presenilins. J. Biol. Chem. 272, 7977-7982.
68. Xia, X., Qian, S., Soriano, S., Wu, Y., Fletcher, A. M., Wang, X. J., Koo, E. H., Wu, X. and 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.
69. Yang, D.-S., Tandon, A., Chen, F., Yu, G., Yu, H., Arawaka, S., Hasegawa, H., Duthie, M., Schmidt, S., Nixon, R., Ramabhadran, T., Mathews, P., Gandy, S., Mount, H., St George-Hyslop, P. and Fraser, P. (2002). Mature glycosylation and trafficking of nicastrin modulate its binding to presenilins. J. Biol. Chem. 277, 28135-28142.
70. Yu, G., Nishimura, M., Arawaka, S., Levitan, D., Zhang, L., Tandon, A., Song, Y. Q., Rogaeva, E., Chen, F., Kawarai, T. et al. (2000). Nicastrin modulates presenilin-mediated notch/glp-1 signal transduction and betaAPP processing. Nature 407, 48-54.
71. Zhang, Z., Nadeau, P., Song, W., Donoviel, D., Yuan, M., Bernstein, A. and Yanker, B. A. (2000). Presenilins are required for gamma-secretase cleavage of beta-APP and transmembrane cleavage of Notch-1. Nat. Cell Biol. 2, 463-465.