Pen-2 is essential for γ-secretase complex stability and trafficking but partially dispensable for endoproteolysis

Biochemistry

Volumn 53, Issue 27, 2014, Pages 4393-4406

  Holmes, Oliver ^a   Paturi, Swetha ^a   Selkoe, Dennis J ^a   Wolfe, Michael S ^a  

^a HARVARD MEDICAL SCHOOL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ACTIVATION ANALYSIS; CELL MEMBRANES; GLYCOPROTEINS; PROTEOLYSIS;

ALZHEIMER'S DISEASE; AMYLOID PRECURSOR PROTEINS; ENDOPROTEOLYSIS; INTRAMEMBRANE PROTEOLYSIS; MUTATIONAL EFFECTS; PROTEOLYTIC ACTIVITIES; SECRETASE COMPLEX; TRANSMEMBRANE DOMAIN;

ENZYME ACTIVITY;

GAMMA SECRETASE; PRESENILIN; PRESENILIN ENHANCER 2; UNCLASSIFIED DRUG;

ANIMAL CELL; ARTICLE; CELL MATURATION; CELL SURFACE; CELLULAR DISTRIBUTION; CONTROLLED STUDY; EMBRYO; ENZYME ACTIVITY; ENZYME LOCALIZATION; ENZYME STABILITY; GENETIC TRANSFECTION; MOUSE; MUTAGENESIS; MUTANT; MUTATION; NONHUMAN; PRIORITY JOURNAL; PROTEIN DEGRADATION; PROTEIN STABILITY;

AMYLOID BETA-PEPTIDES; AMYLOID PRECURSOR PROTEIN SECRETASES; ANIMALS; CELL LINE; GENE KNOCKOUT TECHNIQUES; MICE; MUTATION; PEPTIDE FRAGMENTS; PROTEIN STABILITY; PROTEIN TRANSPORT; PROTEOLYSIS;

EID: 84904342536     PISSN: 00062960     EISSN: 15204995     Source Type: Journal    
DOI: 10.1021/bi500489j     Document Type: Article

References (50)

1. 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
2. Kimberly, W. T., LaVoie, M. J., Ostaszewski, B. L., Ye, W., Wolfe, M. S., and Selkoe, D. J. (2003) γ-Secretase is a membrane protein complex comprised of presenilin, nicastrin, Aph-1, and Pen-2 Proc. Natl. Acad. Sci. U.S.A. 100, 6382-6387
3. Edbauer, D., Winkler, E., Regula, J. T., Pesold, B., Steiner, H., and Haass, C. (2003) Reconstitution of γ-secretase activity Nat. Cell Biol. 5, 486-488
4. 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
5. Brown, M. S., Ye, J., Rawson, R. B., and Goldstein, J. L. (2000) Regulated intramembrane proteolysis: A control mechanism conserved from bacteria to humans Cell 100, 391-398
6. Kopan, R. and Ilagan, M. X. (2004) γ-Secretase: Proteasome of the membrane? Nat. Rev. Mol. Cell Biol. 5, 499-504
7. 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
8. 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
9. 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. Pauwels, K., Williams, T. L., Morris, K. L., Jonckheere, W., Vandersteen, A., Kelly, G., Schymkowitz, J., Rousseau, F., Pastore, A., Serpell, L. C., and Broersen, K. (2012) Structural basis for increased toxicity of pathological Aβ42:Aβ40 ratios in Alzheimer disease J. Biol. Chem. 287, 5650-5660
11. 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
12. 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
13. 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
14. Thinakaran, G., Borchelt, D. R., Lee, M. K., Slunt, H. H., Spitzer, L., Kim, G., Ratovitsky, T., Davenport, F., Nordstedt, C., Seeger, M., Hardy, J., Levey, A. I., Gandy, S. E., Jenkins, N. A., Copeland, N. G., Price, D. L., and Sisodia, S. S. (1996) Endoproteolysis of presenilin 1 and accumulation of processed derivatives in vivo Neuron 17, 181-190
15. Bammens, L., Chavez-Gutierrez, L., Tolia, A., Zwijsen, A., and De Strooper, B. (2011) Functional and topological analysis of Pen-2, the fourth subunit of the γ-secretase complex J. Biol. Chem. 286, 12271-12282
16. Crystal, A. S., Morais, V. A., Pierson, T. C., Pijak, D. S., Carlin, D., Lee, V. M., and Doms, R. W. (2003) Membrane topology of γ-secretase component PEN-2 J. Biol. Chem. 278, 20117-20123
17. 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
18. Kim, S. H. and Sisodia, S. S. (2005) A sequence within the first transmembrane domain of PEN-2 is critical for PEN-2-mediated endoproteolysis of presenilin 1 J. Biol. Chem. 280, 1992-2001
19. Prokop, S., Haass, C., and Steiner, H. (2005) Length and overall sequence of the PEN-2 C-terminal domain determines its function in the stabilization of presenilin fragments J. Neurochem. 94, 57-62
20. 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
21. Prokop, S., Shirotani, K., Edbauer, D., Haass, C., and Steiner, H. (2004) Requirement of PEN-2 for stabilization of the presenilin N-/C-terminal fragment heterodimer within the γ-secretase complex J. Biol. Chem. 279, 23255-23261
22. 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
23. Ahn, K., Shelton, C. C., Tian, Y., Zhang, X., Gilchrist, M. L., Sisodia, S. S., and Li, Y. M. (2010) Activation and intrinsic γ-secretase activity of presenilin 1 Proc. Natl. Acad. Sci. U.S.A. 107, 21435-21440
24. Mao, G., Cui, M. Z., Li, T., Jin, Y., and Xu, X. (2012) Pen-2 is dispensable for endoproteolysis of presenilin 1, and nicastrin-Aph subcomplex is important for both γ-secretase assembly and substrate recruitment J. Neurochem. 123, 837-844
25. Ghanevati, M. and Miller, C. A. (2005) Phospho-β-catenin accumulation in Alzheimer's disease and in aggresomes attributable to proteasome dysfunction J. Mol. Neurosci. 25, 79-94
26. Li, Y. M., Lai, M. T., Xu, M., Huang, Q., DiMuzio-Mower, J., Sardana, M. K., Shi, X. P., Yin, K. C., Shafer, J. A., and Gardell, S. J. (2000) Presenilin 1 is linked with γ-secretase activity in the detergent solubilized state Proc. Natl. Acad. Sci. U.S.A. 97, 6138-6143
27. Fraering, P. C., Ye, W., Strub, J. M., Dolios, G., LaVoie, M. J., Ostaszewski, B. L., van Dorsselaer, A., Wang, R., Selkoe, D. J., and Wolfe, M. S. (2004) Purification and characterization of the human γ-secretase complex Biochemistry 43, 9774-9789
28. Killian, J. A. and von Heijne, G. (2000) How proteins adapt to a membrane-water interface Trends Biochem. Sci. 25, 429-434
29. Richardson, J. S. (1981) The anatomy and taxonomy of protein structure Adv. Protein Chem. 34, 167-339
30. Kimberly, W. T., Esler, W. P., Ye, W., Ostaszewski, B. L., Gao, J., Diehl, T., Selkoe, D. J., and Wolfe, M. S. (2003) Notch and the amyloid precursor protein are cleaved by similar γ-secretase(s) Biochemistry 42, 137-144
31. Campbell, W. A., Reed, M. L., Strahle, J., Wolfe, M. S., and Xia, W. (2003) Presenilin endoproteolysis mediated by an aspartyl protease activity pharmacologically distinct from γ-secretase J. Neurochem. 85, 1563-1574
32. 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
33. Sato, C., Takagi, S., Tomita, T., and Iwatsubo, T. (2008) The C-terminal PAL motif and transmembrane domain 9 of presenilin 1 are involved in the formation of the catalytic pore of the γ-secretase J. Neurosci. 28, 6264-6271
34. Takagi, S., Tominaga, A., Sato, C., Tomita, T., and Iwatsubo, T. (2010) Participation of transmembrane domain 1 of presenilin 1 in the catalytic pore structure of the γ-secretase J. Neurosci. 30, 15943-15950
35. Tolia, A., Chavez-Gutierrez, L., and De Strooper, B. (2006) Contribution of presenilin transmembrane domains 6 and 7 to a water-containing cavity in the γ-secretase complex J. Biol. Chem. 281, 27633-27642
36. 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
37. Dries, D. R., Shah, S., Han, Y. H., Yu, C., Yu, S., Shearman, M. S., and Yu, G. (2009) Glu-333 of nicastrin directly participates in γ-secretase activity J. Biol. Chem. 284, 29714-29724
38. Futai, E., Yagishita, S., and Ishiura, S. (2009) Nicastrin is dispensable for γ-secretase protease activity in the presence of specific presenilin mutations J. Biol. Chem. 284, 13013-13022
39. Zhao, G., Liu, Z., Ilagan, M. X., and Kopan, R. (2010) γ-Secretase composed of PS1/Pen2/Aph1a can cleave notch and amyloid precursor protein in the absence of nicastrin J. Neurosci. 30, 1648-1656
40. Pardossi-Piquard, R., Yang, S. P., Kanemoto, S., Gu, Y., Chen, F., Bohm, C., Sevalle, J., Li, T., Wong, P. C., Checler, F., Schmitt-Ulms, G., St George-Hyslop, P., and Fraser, P. E. (2009) APH1 polar transmembrane residues regulate the assembly and activity of presenilin complexes J. Biol. Chem. 284, 16298-16307
41. Chen, A. C., Guo, L. Y., Ostaszewski, B. L., Selkoe, D. J., and LaVoie, M. J. (2010) Aph-1 associates directly with full-length and C-terminal fragments of γ-secretase substrates J. Biol. Chem. 285, 11378-11391
42. Hasegawa, H., Sanjo, N., Chen, F., Gu, Y. J., Shier, C., Petit, A., Kawarai, T., Katayama, T., Schmidt, S. D., Mathews, P. M., Schmitt-Ulms, G., Fraser, P. E., and St George-Hyslop, P. (2004) Both the sequence and length of the C terminus of PEN-2 are critical for intermolecular interactions and function of presenilin complexes J. Biol. Chem. 279, 46455-46463
43. Bergman, A., Hansson, E. M., Pursglove, S. E., Farmery, M. R., Lannfelt, L., Lendahl, U., Lundkvist, J., and Naslund, J. (2004) Pen-2 is sequestered in the endoplasmic reticulum and subjected to ubiquitylation and proteasome-mediated degradation in the absence of presenilin J. Biol. Chem. 279, 16744-16753
44. Cadwell, K. and Coscoy, L. (2005) Ubiquitination on nonlysine residues by a viral E3 ubiquitin ligase Science 309, 127-130
45. Burr, M. L., van den Boomen, D. J., Bye, H., Antrobus, R., Wiertz, E. J., and Lehner, P. J. (2013) MHC class I molecules are preferentially ubiquitinated on endoplasmic reticulum luminal residues during HRD1 ubiquitin E3 ligase-mediated dislocation Proc. Natl. Acad. Sci. U.S.A. 110, 14290-14295
46. 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
47. Uemura, K., Lill, C. M., Li, X., Peters, J. A., Ivanov, A., Fan, Z., DeStrooper, B., Bacskai, B. J., Hyman, B. T., and Berezovska, O. (2009) Allosteric modulation of PS1/γ-secretase conformation correlates with amyloid β(42/40) ratio PLoS One 4, e7893
48. Fassler, M., Zocher, M., Klare, S., de la Fuente, A. G., Scheuermann, J., Capell, A., Haass, C., Valkova, C., Veerappan, A., Schneider, D., and Kaether, C. (2010) Masking of transmembrane-based retention signals controls ER export of γ-secretase Traffic 11, 250-258
49. Kim, J. H., Johannes, L., Goud, B., Antony, C., Lingwood, C. A., Daneman, R., and Grinstein, S. (1998) Noninvasive measurement of the pH of the endoplasmic reticulum at rest and during calcium release Proc. Natl. Acad. Sci. U.S.A. 95, 2997-3002
50. Baulac, S., LaVoie, M. J., Kimberly, W. T., Strahle, J., Wolfe, M. S., Selkoe, D. J., and Xia, W. (2003) Functional gamma-secretase complex assembly in Golgi/trans-Golgi network: Interactions among presenilin, nicastrin, Aph1, Pen-2, and γ-secretase substrates Neurobiol. Dis. 14, 194-204