Activation and intrinsic γ-secretase activity of presenilin 1

Proceedings of the National Academy of Sciences of the United States of America

Volumn 107, Issue 50, 2010, Pages 21435-21440

  Ahn, Kwangwook ^a   Shelton, Christopher C ^a,b   Tian, Yuan ^a,b   Zhang, Xulun ^c   Gilchrist, M Lane ^a,d   Sisodia, Sangram S ^c   Li, Yue Ming ^a,b  

^a MEMORIAL SLOAN KETTERING CANCER CENTER   (United States)

^b Weill Cornell Graduate School of Biomedical Sciences   (United States)

^c UNIVERSITY OF CHICAGO   (United States)

^d City University of New York   (United States)

Author keywords

Intermembrane cleaving proteases; Notch; Presenilinase; Reconstitution

Indexed keywords

GAMMA SECRETASE; GAMMA SECRETASE INHIBITOR; PRESENILIN 1;

ALZHEIMER DISEASE; ARTICLE; ENZYME ACTIVATION; ENZYME ACTIVITY; ENZYME SYNTHESIS; PRIORITY JOURNAL; PROTEIN CLEAVAGE; PROTEIN DEGRADATION;

ALZHEIMER DISEASE; AMYLOID BETA-PEPTIDES; AMYLOID BETA-PROTEIN PRECURSOR; AMYLOID PRECURSOR PROTEIN SECRETASES; ENZYME ACTIVATION; HUMANS; MEMBRANE PROTEINS; MUTATION; PEPTIDE FRAGMENTS; PRESENILIN-1; PROTEIN SUBUNITS; PROTEOLIPIDS; RECOMBINANT PROTEINS;

EID: 78650718960     PISSN: 00278424     EISSN: 10916490     Source Type: Journal    
DOI: 10.1073/pnas.1013246107     Document Type: Article

References (46)

1. De Strooper B (2003) Aph-1, Pen-2, and nicastrin with presenilin generate an active gamma-secretase complex. Neuron 38:9-12.
2. Edbauer D, et al. (2003) Reconstitution of gamma-secretase activity. Nat Cell Biol 5:486-488.
3. Thinakaran G, et al. (1996) Endoproteolysis of presenilin 1 and accumulation of processed derivatives in vivo. Neuron 17:181-190.
4. Takasugi N, et al. (2003) The role of presenilin cofactors in the gamma-secretase complex. Nature 422:438-441.
5. Luo WJ, et al. (2003) PEN-2 and APH-1 coordinately regulate proteolytic processing of presenilin 1. J Biol Chem 278:7850-7854.
6. Zhang YW, et al. (2005) Nicastrin is critical for stability and trafficking but not association of other presenilin/gamma-secretase components. J Biol Chem 280:17020-17026.
7. Kim SH, Ikeuchi T, Yu C, Sisodia SS (2003) Regulated hyperaccumulation of presenilin-1 and the "gamma-secretase" complex. Evidence for differential intramembranous processing of transmembrane subatrates. J Biol Chem 278:33992-34002.
8. Shah S, et al. (2005) Nicastrin functions as a gamma-secretase-substrate receptor. Cell 122:435-447.
9. Chavez-Gutierrez L, et al. (2008) Glu(332) in the Nicastrin ectodomain is essential for gamma-secretase complex maturation but not for its activity. J Biol Chem 283:20096-20105.
10. Zhao G, Liu Z, Ilagan MX, Kopan R (2010) Gamma-secretase composed of PS1/Pen2/ Aph1a can cleave notch and amyloid precursor protein in the absence of nicastrin. J Neurosci 30:1648-1656.
11. Wolfe MS, et al. (1999) Two transmembrane aspartates in presenilin-1 required for presenilin endoproteolysis and gamma-secretase activity. Nature 398:513-517.
12. Fukumori A, Fluhrer R, Steiner H, Haass C (2010) Three-amino acid spacing of presenilin endoproteolysis suggests a general stepwise cleavage of gamma-secretase-mediated intramembrane proteolysis. J Neurosci 30:7853-7862.
13. Campbell WA, Reed ML, Strahle J, Wolfe MS, Xia W (2003) Presenilin endoproteolysis mediated by an aspartyl protease activity pharmacologically distinct from gammasecretase. J Neurochem 85:1563-1574.
14. Nyabi O, et al. (2003) Presenilins mutated at Asp-257 or Asp-385 restore Pen-2 expression and nicastrin glycosylation but remain catalytically inactive in the absence of wild type presenilin. J Biol Chem 278:43430-43436.
15. De Strooper B, et al. (1998) Deficiency of presenilin-1 inhibits the normal cleavage of amyloid precursor protein. Nature 391:387-390.
16. Naruse S, et al. (1998) Effects of PS1 deficiency on membrane protein trafficking in neurons. Neuron 21:1213-1221.
17. Esler WP, et al. (2000) Transition-state analogue inhibitors of gamma-secretase bind directly to presenilin-1. Nat Cell Biol 2:428-434.
18. Li YM, et al. (2000) Photoactivated gamma-secretase inhibitors directed to the active site covalently label presenilin 1. Nature 405:689-694.
19. Lei X, Ahn K, Zhu L, Ubarretxena-Belandia I, Li YM (2008) Soluble oligomers of the intramembrane serine protease YqgP are catalytically active in the absence of detergents. Biochemistry 47:11920-11929.
20. Ikeuchi T, Dolios G, Kim SH, Wang R, Sisodia SS (2003) Familial Alzheimer diseaselinked presenilin 1 variants enhance production of both Abeta 1-40 and Abeta 1-42 peptides that are only partially sensitive to a potent aspartyl protease transition state inhibitor of "gamma-secretase". J Biol Chem 278:7010-7018.
21. Steiner H, et al. (1999) The biological and pathological function of the presenilin-1 Deltaexon 9 mutation is independent of its defect to undergo proteolytic processing. J Biol Chem 274:7615-7618.
22. Shelton CC, Tian Y, Frattini MG, Li YM (2009) An exo-cell assay for examining real-time gamma-secretase activity and inhibition. Mol Neurodegener 4:22.
23. Tian Y, Crump CJ, Li YM(2010) Dual role of {alpha}-secretase cleavage in the regulation of {gamma}-secretase activity for amyloid production. J Biol Chem 285:32549-32556.
24. Shearman MS, et al. (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.
25. Chun J, Yin YI, Yang G, Tarassishin L, Li YM (2004) Stereoselective synthesis of photoreactive peptidomimetic gamma-secretase inhibitors. J Org Chem 69:7344-7347.
26. Shelton CC, et al. (2009) Modulation of gamma-secretase specificity using small molecule allosteric inhibitors. Proc Natl Acad Sci USA 106:20228-20233.
27. Tian Y, Bassit B, Chau D, Li YM (2010) An APP inhibitory domain containing the Flemish mutation residue modulates gamma-secretase activity for Abeta production. Nat Struct Mol Biol 17:151-158.
28. Placanica L, Zhu L, Li YM (2009) Gender- and age-dependent gamma-secretase activity in mouse brain and its implication in sporadic Alzheimer disease. PLoS ONE 4:e5088.
29. Bayerl TM, Bloom M (1990) Physical properties of single phospholipid bilayers adsorbed to micro glass beads. A new vesicular model system studied by 2H-nuclear magnetic resonance. Biophys J 58:357-362.
30. Kumar-Singh S, et al. (2006) Mean age-of-onset of familial alzheimer disease caused by presenilin mutations correlates with both increased Abeta42 and decreased Abeta40. Hum Mutat 27:686-695.
31. Steiner H, 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.
32. Moehlmann T, et al. (2002) Presenilin-1 mutations of leucine 166 equally affect the generation of the Notch and APP intracellular domains independent of their effect on Abeta 42 production. Proc Natl Acad Sci USA 99:8025-8030.
33. Citron M, et al. (1998) Additive effects of PS1 and APP mutations on secretion of the 42-residue amyloid beta-protein. Neurobiol Dis 5:107-116.
34. Levitan D, et al. (2001) PS1 N- and C-terminal fragments form a complex that functions in APP processing and Notch signaling. Proc Natl Acad Sci USA 98:12186-12190.
35. Bentahir M, et al. (2006) Presenilin clinical mutations can affect gamma-secretase activity by different mechanisms. J Neurochem 96:732-742.
36. Kounnas MZ, et al. (2010) Modulation of γ-secretase reduces β-amyloid deposition in a transgenic mouse model of Alzheimer's disease. Neuron 67:769-780.
37. Borchelt DR, et al. (1996) Familial Alzheimer's disease-linked presenilin 1 variants elevate Abeta1-42/1-40 ratio in vitro and in vivo. Neuron 17:1005-1013.
38. Scheuner D, et al. (1996) Secreted amyloid beta-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.
39. Suzuki N, et al. (1994) An increased percentage of long amyloid beta protein secreted by familial amyloid beta protein precursor (beta APP717) mutants. Science 264:1336-1340.
40. Yin YI, et al. (2007) {gamma}-secretase substrate concentration modulates the Abeta42/ Abeta40 ratio: Implications for Alzheimer disease. J Biol Chem 282:23639-23644.
41. Lichtenthaler SF, et al. (1999) Mechanism of the cleavage specificity of Alzheimer's disease gamma-secretase identified by phenylalanine-scanning mutagenesis of the transmembrane domain of the amyloid precursor protein. Proc Natl Acad Sci USA 96:3053-3058.
42. Steiner H, et al. (1999) Amyloidogenic function of the Alzheimer's disease-associated presenilin 1 in the absence of endoproteolysis. Biochemistry 38:14600-14605.
43. Kim SH, Sisoda SS (2005) Evidence that the "NF" mofit in transmembrane domain 4 of presenilin 1 is critical for binding with PEN-2. J Biol Chem 280:41953-41966.
44. Knappenberger KS, et al. (2004) Mechanism of gamma-secretase cleavage activation: Is gamma-secretase regulated through autoinhibition involving the presenilin-1 exon 9 loop? Biochemistry 43:6208-6218.
45. Xia W, et al. (2000) Presenilin complexes with the C-terminal fragments of amyloid precursor protein at the sites of amyloid beta-protein generation. Proc Natl Acad Sci USA 97:9299-9304.
46. Li YM, et al. (2000) Presenilin 1 is linked with gamma-secretase activity in the detergent solubilized state. Proc Natl Acad Sci USA 97:6138-6143.