Deletion of presenilin 1 hydrophilic loop sequence leads to impaired γ-secretase activity and exacerbated amyloid pathology

Journal of Neuroscience

Volumn 26, Issue 14, 2006, Pages 3845-3854

  Deng, Yu ^a   Tarassishin, Leonid ^b   Kallhoff, Verena ^a   Peethumnongsin, Erica ^a   Wu, Ling ^a   Li, Yue Ming ^b   Zheng, Hui ^a  

^a BAYLOR COLLEGE OF MEDICINE   (United States)

^b MEMORIAL SLOAN KETTERING CANCER CENTER   (United States)

Author keywords

secretase; Alzheimer's disease; Amyloid peptides; Homodimer; Knock in mice; Presenilin

Indexed keywords

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

ALZHEIMER DISEASE; AMINO ACID SEQUENCE; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CONTROLLED STUDY; DISEASE EXACERBATION; ENZYME ACTIVITY; EXON; HOMOZYGOSITY; HYDROPHILICITY; MOUSE; NONHUMAN; NUCLEOTIDE SEQUENCE; PATHOGENESIS; PRIORITY JOURNAL; PROTEIN DEGRADATION; PROTEIN DOMAIN; PROTEIN FUNCTION; PROTEIN PROCESSING;

AMINO ACID SEQUENCE; AMYLOID BETA-PROTEIN; AMYLOID PRECURSOR PROTEIN SECRETASES; ANIMALS; ASPARTIC ENDOPEPTIDASES; BRAIN; ENDOPEPTIDASES; ENZYME ACTIVATION; MEMBRANE PROTEINS; MICE; MICE, KNOCKOUT; MOLECULAR SEQUENCE DATA; MUTAGENESIS, SITE-DIRECTED; PRESENILIN-1; PROTEIN STRUCTURE, TERTIARY; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 33645578379     PISSN: 02706474     EISSN: 02706474     Source Type: Journal    
DOI: 10.1523/JNEUROSCI.5384-05.2006     Document Type: Article

References (51)

1. Annaert W, De Strooper B (2002) A cell biological perspective on Alzheimer's disease. Annu Rev Cell Dev Biol 18:25-51.
2. Baki L, Marambaud P, Efthimiopoulos S, Georgakopoulos A, Wen P, Cui W, Shioi J, Koo E, Ozawa M, Friedrich VL Jr, Robakis NK (2001) Presenilin-1 binds cytoplasmic epithelial cadherin, inhibits cadherin/p120 association, and regulates stability and function of the cadherin/catenin adhesion complex. Proc Natl Acad Sci USA 98:2381-2386.
3. Berezovska O, Lleo A, Herl LD, Frosch MP, Stern EA, Bacskai BJ, Hyman BT (2005) Familial Alzheimer's disease presenilin 1 mutations cause alterations in the conformation of presenilin and interactions with amyloid precursor protein. J Neurosci 25:3009-3017.
4. Brown MS, Ye J, Rawson RB, Goldstein JL (2000) Regulated intramembrane proteolysis: a control mechanism conserved from bacteria to humans. Cell 100:391-398.
5. Cervantes S, Saura CA, Pomares E, Gonzalez-Duarte R, Marfany G (2004) Functional implications of the presenilin dimerization: reconstitution of gamma-secretase activity by assembly of a catalytic site at the dimer interface of two catalytically inactive presenilins. J Biol Chem 279:36519-36529.
6. Chen F, Gu Y, Hasegawa H, Ruan X, Arawaka S, Fraser P, Westaway D, Mount H, St George-Hyslop P (2002) Presenilin 1 mutations activate gamma 42-secretase but reciprocally inhibit epsilon-secretase cleavage of amyloid precursor protein (APP) and S3-cleavage of notch. J Biol Chem 277:36521-36526.
7. De Strooper B, Annaert W, Cupers P, Saftig P, Craessaerts K, Mumm JS, Schroeter EH, Schrijvers V, Wolfe MS, Ray WJ, Goate A, Kopan R (1999) A presenilin-1-dependent gamma-secretase-like protease mediates release of Notch intracellular domain. Nature 398:518-522.
8. Dewachter I, Reverse D, Caluwaerts N, Ris L, Kuiperi C, Van den Haute C, Spittaels K, Umans L, Serneels L, Thiry E, Moechars D, Mercken M, Godaux E, Van Leuven F (2002) Neuronal deficiency of presenilin 1 inhibits amyloid plaque formation and corrects hippocampal long-term potentiation but not a cognitive defect of amyloid precursor protein [V717I] transgenic mice. J Neurosci 22:3445-3453.
9. Donoviel DB, Hadjantonakis AK, Ikeda M, Zheng H, Hyslop PS, Bernstein A (1999) Mice lacking both presenilin genes exhibit early embryonic patterning defects. Genes Dev 13:2801-2810.
10. Esler WP, Kimberly WT, Ostaszewski BL, Diehl TS, Moore CL, Tsai JY, Rahmati T, Xia W, Selkoe DJ, Wolfe MS (2000) Transition-state analogue inhibitors of gamma-secretase bind directly to presenilin-1. Nat Cell Biol 2:428-434.
11. Georgakopoulos A, Marambaud P, Efthimiopoulos S, Shioi J, Cui W, Li HC, Schutte M, Gordon R, Holstein GR, Martinelli G, Mehta P, Friedrich Jr VL, Robakis NK (1999) Presenilin-1 forms complexes with the cadherin/catenin cell-cell adhesion system and is recruited to intercellular and synaptic contacts. Mol Cell 4:893-902.
12. Gu Y, Sanjo N, Chen F, Hasegawa H, Petit A, Ruan X, Li W, Shier C, Kawarai T, Schmitt-Ulms G, Westaway D, St. George-Hyslop P, Fraser PE (2004) The presenilin proteins are components of multiple membrane-bound complexes that have different biological activities. J Biol Chem 279:31329-31336.
13. Gupta-Rossi N, Le Bail O, Gonen H, Brou C, Logeat F, Six E, Ciechanover A, Israel A (2001) Functional interaction between SEL-10, an F-box protein, and the nuclear form of activated Notch1 receptor. J Biol Chem 276:34371-34378.
14. Herreman A, Hartmann D, Annaert W, Saftig P, Craessaerts K, Serneels L, Umans L, Schrijvers V, Checler F, Vanderstichele H, Baekelandt V, Dressel R, Cupers P, Huylebroeck D, Zwijsen A, Van Leuven F, De Strooper B (1999) Presenilin 2 deficiency causes a mild pulmonary phenotype and no changes in amyloid precursor protein processing but enhances the embryonic lethal phenotype of presenilin 1 deficiency. Proc Natl Acad Sci USA 96:11872-11877.
15. Hsiao K, Chapman P, Nilsen S, Eckman C, Harigaya Y, Younkin S, Yang F, Cole G (1996) Correlative memory deficits, Aβ elevation, and amyloid plaques in transgenic mice. Science 274:99-102.
16. Iwatsubo T (2004) The γ-secretase complex: machinery for intramembrane proteolysis. Curr Opin Neurobiol 14:379-383.
17. Iwatsubo T, Odaka A, Suzuki N, Mizusawa H, Nukina N, 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.
18. Jankowsky JL, Slunt HH, Gonzales V, Jenkins NA, Copeland NG, Borchelt DR (2004) APP processing and amyloid deposition in mice haploinsufficient for presenilin 1. Neurobiol Aging 25:885-892.
19. Kang DE, Soriano S, Frosch MP, Collins T, Naruse S, Sisodia SS, Leibowitz G, Levine F, Koo EH (1999) Presenilin 1 facilitates the constitutive turnover of β-catenin: differential activity of Alzheimer's disease-linked PS1 mutants in β-catenin-signaling pathway. J Neurosci 19:4229-4237.
20. Kang DE, Soriano S, Xia X, Eberhart CG, De Strooper B, Zheng H, Koo EH (2002) Presenilin couples the paired phosphorylation of β-catenin independent of axin: implications for β-catenin activation in tumorigenesis. Cell 110:751-762.
21. Kirschenbaum F, Hsu SC, Cordell B, McCarthy JV (2001) Substitution of a glycogen synthase kinase-3β phosphorylation site in presenilin 1 separates presenilin function from β-catenin signaling. J Biol Chem 276:7366-7375.
22. Koepp DM, Schaefer LK, Ye X, Keyomarsi K, Chu C, Harper JW, Elledge SJ (2001) Phosphorylation-dependent ubiquitination of cyclin E by the SCFFbw7 ubiquitin ligase. Science 294:173-177.
23. Kopan R, Ilagan MX (2004) γ-secretase: proteasome of the membrane? Nat Rev Mol Cell Biol 5:499-504.
24. Kulic L, Walter J, Multhaup G, Teplow DB, Baumeister R, Romig H, Capell A, Steiner H, Haass C (2000) Separation of presenilin function in amyloid β-peptide generation and endoproteolysis of Notch. Proc Natl Acad Sci USA 97:5913-5918.
25. Li YM, Lai MT, Xu M, Huang Q, DiMuzio-Mower J, Sardana MK, Shi XP, Yin KC, Shafer JA, Gardell SJ (2000a) Presenilin 1 is linked with γ-secretase activity in the detergent solubilized state. Proc Natl Acad Sci USA 97:6138-6143.
26. Li YM, Xu M, Lai MT, Huang Q, Castro JL, DiMuzio-Mower J, Harrison T, Lellis C, Nadin A, Neduvelil JG, Register RB, Sardana MK, Shearman MS, Smith AL, Shi XP, Yin KC, Shafer JA, Gardell SJ (2000b) Photoactivated γ-secretase inhibitors directed to the active site covalently label presenilin 1. Nature 405:689-694.
27. Marambaud P, Shioi J, Serban G, Georgakopoulos A, Sarner S, Nagy V, Baki L, Wen P, Efthimiopoulos S, Shao Z, Wisniewski T, Robakis NK (2002) A presenilin-1/γ-secretase cleavage releases the E-cadherin intracellular domain and regulates disassembly of adherens junctions. EMBO J 21:1948-1956.
28. Marambaud P, Wen PH, Dutt A, Shioi J, Takashima A, Siman R, Robakis NK (2003) A CBP binding transcriptional repressor produced by the PS1/ε-cleavage of N-cadherin is inhibited by PS1 FAD mutations. Cell 114:635-645.
29. McGowan E, Pickford F, Kim J, Onstead L, Eriksen J, Yu C, Skipper L, Murphy MP, Beard J, Das P, Jansen K, Delucia M, Lin WL, Dolios G, Wang R, Eckman CB, Dickson DW, Hutton M, Hardy J, Golde T (2005) Aβ42 is essential for parenchymal and vascular amyloid deposition in mice. Neuron 47:191-199.
30. Moehlmann T, Winkler E, Xia X, Edbauer D, Murrell J, Capell A, Kaether C, Zheng H, Ghetti B, Haass C, Steiner H (2002) Presenilin-1 mutations of leucine 166 equally affect the generation of the Notch and APP intracellular domains independent of their effect on Aβ42 production. Proc Natl Acad Sci USA 99:8025-8030.
31. Nicolas M, Wolfer A, Raj K, Kummer JA, Mill P, van Noort M, Hui CC, Clevers H, Dotto GP, Radtke F (2003) Notch1 functions as a tumor suppressor in mouse skin. Nat Genet 33:416-421.
32. Qyang Y, Chambers SM, Wang P, Xia X, Chen X, Goodell MA, Zheng H (2004) Myeloproliferative disease in mice with reduced presenilin gene dosage: effect of γ-secretase blockage. Biochemistry 43:5352-5359.
33. Saura CA, Tomita T, Davenport F, Harris CL, Iwatsubo T, Thinakaran G (1999) Evidence that intramolecular associations between presenilin domains are obligatory for endoproteolytic processing. J Biol Chem 274:13818-13823.
34. Saura CA, Tomita T, Soriano S, Takahashi M, Leem JY, Honda T, Koo EH, Iwatsubo T, Thinakaran G (2000) The nonconserved hydrophilic loop domain of presenilin (PS) is not required for PS endoproteolysis or enhanced Aβ42 production mediated by familial early onset Alzheimer's disease-linked PS variants. J Biol Chem 275:17136-17142.
35. Saura CA, Chen G, Malkani S, Choi SY, Takahashi RH, Zhang D, Gouras GK, Kirkwood A, Morris RG, Shen J (2005) Conditional inactivation of presenilin 1 prevents amyloid accumulation and temporarily rescues contextual and spatial working memory impairments in amyloid precursor protein transgenic mice. J Neurosci 25:6755-6764.
36. Schroeter EH, Ilagan MX, Brunkan AL, Hecimovic S, Li YM, Xu M, Lewis HD, Saxena MT, De Strooper B, Coonrod A, Tomita T, Iwatsubo T, Moore CL, Goate A, Wolfe MS, Shearman M, Kopan R (2003) A presenilin dimer at the core of the γ-secretase enzyme: insights from parallel analysis of Notch 1 and APP proteolysis. Proc Natl Acad Sci USA 100:13075-13080.
37. Shah S, Lee SF, Tabuchi K, Hao YH, Yu C, LaPlant Q, Ball H, Dann III CE, Sudhof T, Yu G (2005) Nicastrin functions as a γ-secretase-substrate receptor. Cell 122:435-447.
38. Siman R, Reaume AG, Savage MJ, Trusko S, Lin YG, Scott RW, Flood DG (2000) Presenilin-1 P264L knock-in mutation: differential effects on Aβ production, amyloid deposition, and neuronal vulnerability. J Neurosci 20:8717-8726.
39. Song W, Nadeau P, Yuan M, Yang X, Shen J, Yankner BA (1999) Proteolytic release and nuclear translocation of Notch-1 are induced by presenilin-1 and impaired by pathogenic presenilin-1 mutations. Proc Natl Acad Sci USA 96:6959-6963.
40. Soriano S, Kang DE, Fu M, Pestell R, Chevallier N, Zheng H, Koo EH (2001) Presenilin 1 negatively regulates β-catenin/T cell factor/lymphoid enhancer factor-1 signaling independently of β-amyloid precursor protein and notch processing. J Cell Biol 152:785-794.
41. Tarassishin L, Yin YI, Bassit B, Li YM (2004) Processing of Notch and amyloid precursor protein by γ-secretase is spatially distinct. Proc Natl Acad Sci USA 101:17050-17055.
42. Tetzlaff MT, Yu W, Li M, Zhang P, Finegold M, Mahon K, Harper JW, Schwartz RJ, Elledge SJ (2004) Defective cardiovascular development and elevated cyclin E and Notch proteins in mice lacking the Fbw7 F-box protein. Proc Natl Acad Sci USA 101:3338-3345.
43. Thinakaran G (1999) The role of presenilins in Alzheimer's disease. J Clin Invest 104:1321-1327.
44. Tournoy J, Bossuyt X, Snellinx A, Regent M, Garmyn M, Serneels L, Saftig P, Craessaerts K, De Strooper B, Hartmann D (2004) Partial loss of presenilins causes seborrheic keratosis and autoimmune disease in mice. Hum Mol Genet 13:1321-1331.
45. Wiley JC, Hudson M, Kanning KC, Schecterson LC, Bothwell M (2005) Familial Alzheimer's disease mutations inhibit γ-secretase-mediated liberation of β-amyloid precursor protein carboxy-terminal fragment. J Neurochem 94:1189-1201.
46. Wolfe MS, Xia W, Ostaszewski BL, Diehl TS, Kimberly WT, Selkoe DJ (1999) Two transmembrane aspartates in presenilin-1 required for presenilin endoproteolysis and γ-secretase activity. Nature 398:513-517.
47. Wu G, Hubbard EJ, Kitajewski JK, Greenwald I (1998) Evidence for functional and physical association between Caenorhabditis elegans SEL-10, a Cdc4p-related protein, and SEL-12 presenilin. Proc Natl Acad Sci USA 95:15787-15791.
48. Xia X, Qian S, Soriano S, Wu Y, Fletcher AM, Wang X-J, Koo EH, Wu X, Zheng H (2001) Loss of presenilin 1 is associated with enhanced β-catenin signaling and skin tumorigenesis. Proc Natl Acad Sci USA 98:10863-10868.
49. Xia X, Wang P, Sun X, Soriano S, Shum WK, Yamaguchi H, Trumbauer ME, Takashima A, Koo EH, Zheng H (2002) The aspartate-257 of presenilin 1 is indispensable for mouse development and production of β-amyloid peptides through β-catenin-independent mechanisms. Proc Natl Acad Sci USA 99:8760-8765.
50. Yan R, Bienkowski MJ, Shuck ME, Miao H, Tory MC, Pauley AM, Brashier JR, Stratman NC, Mathews WR, Buhl AE, Carter DB, Tomasselli AG, Parodi LA, Heinrikson RL, Gurney ME (1999) Membrane-anchored aspartyl protease with Alzheimer's disease β-secretase activity. Nature 402:533-537.
51. Yu G, Chen F, Levesque G, Nishimura M, Zhang DM, Levesque L, Rogaeva E, Xu D, Liang Y, Duthie M, St George-Hyslop PH, Fraser PE (1998) The presenilin 1 protein is a component of a high molecular weight intracellular complex that contains β-catenin. J Biol Chem 273:16470-16475.