Changed membrane integration and catalytic site conformation are two mechanisms behind the increased Aβ42/Aβ40 ratio by presenilin 1 familial Alzheimer-linked mutations

FEBS Open Bio

Volumn 4, Issue , 2014, Pages 393-406

  Wanngren, Johanna ^a   Lara, Patricia ^b   Öjemalm, Karin ^b   Maioli, Silvia ^a   Moradi, Nasim ^b   Chen, Lu ^b   Tjernberg, Lars O ^a   Lundkvist, Johan ^a   Nilsson, IngMarie ^b   Karlström, Helena ^a  

^a KAROLINSKA INSTITUTE   (Sweden)

^b STOCKHOLM UNIVERSITY   (Sweden)

Author keywords

Alzheimer disease; Amyloid peptide; Membrane integration; Protein structure; Secretase

Indexed keywords

AMYLOID BETA PROTEIN[1-40]; AMYLOID BETA PROTEIN[1-42]; AMYLOID PRECURSOR PROTEIN; FLAVINE ADENINE NUCLEOTIDE; GAMMA SECRETASE; PRESENILIN 1;

ARTICLE; ENZYME ACTIVITY; GENE MUTATION; HYDROPHOBICITY; PRIORITY JOURNAL; PROTEIN CONFORMATION; PROTEIN PROCESSING; ALZHEIMER DISEASE; CONTROLLED STUDY; DNA FLANKING REGION; ENZYME ACTIVE SITE; ENZYME CONFORMATION; FAMILIAL ALZHEIMER DISEASE; MEMBRANE BIOLOGY; PHENOTYPE;

EID: 84899823053     PISSN: 22115463     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.fob.2014.04.006     Document Type: Article

References (71)

1. Masters C.L., Simms G., Weinman N.A., Multhaup G., McDonald B.L., Beyreuther K. Amyloid plaque core protein in Alzheimer disease and Down syndrome. Proc. Natl. Acad. Sci. U.S.A. 1985, 82:4245-4249.
2. Masters C.L., Selkoe D.J. Biochemistry of amyloid beta-protein and amyloid deposits in Alzheimer disease. Cold Spring Harb. Perspect. Med. 2012, 2:a006262.
3. Esler W.P., Wolfe M.S. A portrait of Alzheimer secretases - new features and familiar faces. Science 2001, 293:1449-1454.
4. Czirr E., Cottrell B.A., Leuchtenberger S., Kukar T., Ladd T.B., Esselmann H., Paul S., Schubenel R., Torpey J.W., Pietrzik C.U., Golde T.E., Wiltfang J., Baumann K., Koo E.H., Weggen S. Independent generation of Abeta42 and Abeta38 peptide species by gamma-secretase. J. Biol. Chem. 2008, 283:17049-17054.
5. Kakuda N., Funamoto S., Yagishita S., Takami M., Osawa S., Dohmae N., Ihara Y. Equimolar production of amyloid beta-protein and amyloid precursor protein intracellular domain from beta-carboxyl-terminal fragment by gamma-secretase. J. Biol. Chem. 2006, 281:14776-14786.
6. Qi-Takahara Y., Morishima-Kawashima M., Tanimura Y., Dolios G., Hirotani N., Horikoshi Y., Kametani F., Maeda M., Saido T.C., Wang R., Ihara Y. Longer forms of amyloid beta protein: implications for the mechanism of intramembrane cleavage by gamma-secretase. J. Neurosci. 2005, 25:436-445.
7. Lesne S., Koh M.T., Kotilinek L., Kayed R., Glabe C.G., Yang A., Gallagher M., Ashe K.H. A specific amyloid-beta protein assembly in the brain impairs memory. Nature 2006, 440:352-357.
8. Walsh D.M., Klyubin I., Fadeeva J.V., Cullen W.K., Anwyl R., Wolfe M.S., Rowan M.J., Selkoe D.J. Naturally secreted oligomers of amyloid beta protein potently inhibit hippocampal long-term potentiation in vivo. Nature 2002, 416:535-539.
9. Shankar G.M., Li S., Mehta T.H., Garcia-Munoz A., Shepardson N.E., Smith I., Brett F.M., Farrell M.A., Rowan M.J., Lemere C.A., Regan C.M., Walsh D.M., Sabatini B.L., Selkoe D.J. Amyloid-beta protein dimers isolated directly from Alzheimer's brains impair synaptic plasticity and memory. Nat. Med. 2008, 14:837-842.
10. Brown M.S., Ye J., Rawson R.B., Goldstein J.L. Regulated intramembrane proteolysis: a control mechanism conserved from bacteria to humans. Cell 2000, 100:391-398.
11. Francis R., McGrath G., Zhang J., Ruddy D.A., Sym M., Apfeld J., Nicoll M., Maxwell M., Hai B., Ellis M.C., Parks A.L., Xu W., Li J., Gurney M., Myers R.L., Himes C.S., Hiebsch R., Ruble C., Nye J.S., Curtis D. Aph-1 and pen-2 are required for Notch pathway signaling, gamma-secretase cleavage of betaAPP, and presenilin protein accumulation. Dev. Cell 2002, 3:85-97.
12. Goutte C., Tsunozaki M., Hale V.A., Priess J.R. APH-1 is a multipass membrane protein essential for the Notch signaling pathway in Caenorhabditis elegans embryos. Proc. Natl. Acad. Sci. U.S.A. 2002, 99:775-779.
13. Wolfe M.S., Xia W., Ostaszewski B.L., Diehl T.S., Kimberly W.T., Selkoe D.J. Two transmembrane aspartates in presenilin-1 required for presenilin endoproteolysis and gamma-secretase activity. Nature 1999, 398:513-517.
14. Yu G., Nishimura M., Arawaka S., Levitan D., Zhang L., Tandon A., Song Y.Q., Rogaeva E., Chen F., Kawarai T., Supala A., Levesque L., Yu H., Yang D.S., Holmes E., Milman P., Liang Y., Zhang D.M., Xu D.H., Sato C., Rogaev E., Smith M., Janus C., Zhang Y., Aebersold R., Farrer L.S., Sorbi S., Bruni A., Fraser P., St.George-Hyslop P. Nicastrin modulates presenilin-mediated notch/glp-1 signal transduction and betaAPP processing. Nature 2000, 407:48-54.
15. Henricson A., Kall L., Sonnhammer E.L. A novel transmembrane topology of presenilin based on reconciling experimental and computational evidence. FEBS J. 2005, 272:2727-2733.
16. Laudon H., Hansson E.M., Melen K., Bergman A., Farmery M.R., Winblad B., Lendahl U., von Heijne G., Naslund J. A nine-transmembrane domain topology for presenilin 1. J. Biol. Chem. 2005, 280:35352-35360.
17. Oh Y.S., Turner R.J. Topology of the C-terminal fragment of human presenilin 1. Biochemistry 2005, 44:11821-11828.
18. Spasic D., Tolia A., Dillen K., Baert V., De Strooper B., Vrijens S., Annaert W. Presenilin-1 maintains a nine-transmembrane topology throughout the secretory pathway. J. Biol. Chem. 2006, 281:26569-26577.
19. 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., Sisodia S.S. Endoproteolysis of presenilin 1 and accumulation of processed derivatives in vivo. Neuron 1996, 17:181-190.
20. Scheuner D., Eckman C., Jensen M., Song X., Citron M., Suzuki N., Bird T.D., Hardy J., Hutton M., Kukull W., Larson E., Levy-Lahad E., Viitanen M., Peskind E., Poorkaj P., Schellenberg G., Tanzi R., Wasco W., Lannfelt L., Selkoe D., Younkin S. 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. 1996, 2:864-870.
21. Kumar-Singh S., Theuns J., Van Broeck B., Pirici D., Vennekens K., Corsmit E., Cruts M., Dermaut B., Wang R., Van Broeckhoven C. Mean age-of-onset of familial alzheimer disease caused by presenilin mutations correlates with both increased Abeta42 and decreased Abeta40. Hum. Mutat. 2006, 27:686-695.
22. Bentahir M., Nyabi O., Verhamme J., Tolia A., Horre K., Wiltfang J., Esselmann H., De Strooper B. Presenilin clinical mutations can affect gamma-secretase activity by different mechanisms. J. Neurochem. 2006, 96:732-742.
23. Citron M., Westaway D., Xia W., Carlson G., Diehl T., Levesque G., Johnson-Wood K., Lee M., Seubert P., Davis A., Kholodenko D., Motter R., Sherrington R., Perry B., Yao H., Strome R., Lieberburg I., Rommens J., Kim S., Schenk D., Fraser P., St.George Hyslop P., Selkoe D.J. Mutant presenilins of Alzheimer's disease increase production of 42-residue amyloid beta-protein in both transfected cells and transgenic mice. Nat. Med. 1997, 3:67-72.
24. Kretner B., Fukumori A., Gutsmiedl A., Page R.M., Luebbers T., Galley G., Baumann K., Haass C., Steiner H. Attenuated Abeta42 responses to low potency gamma-secretase modulators can be overcome for many pathogenic presenilin mutants by second-generation compounds. J. Biol. Chem. 2011, 286:15240-15251.
25. Takami M., Nagashima Y., Sano Y., Ishihara S., Morishima-Kawashima M., Funamoto S., Ihara Y. gamma-Secretase: successive tripeptide and tetrapeptide release from the transmembrane domain of beta-carboxyl terminal fragment. J. Neurosci. 2009, 29:13042-13052.
26. Chavez-Gutierrez L., Bammens L., Benilova I., Vandersteen A., Benurwar M., Borgers M., Lismont S., Zhou L., Van Cleynenbreugel S., Esselmann H., Wiltfang J., Serneels L., Karran E., Gijsen H., Schymkowitz J., Rousseau F., Broersen K., De Strooper B. The mechanism of gamma-Secretase dysfunction in familial Alzheimer disease. EMBO J. 2012, 31:2261-2274.
27. Kim J., Onstead L., Randle S., Price R., Smithson L., Zwizinski C., Dickson D.W., Golde T., McGowan E. Abeta40 inhibits amyloid deposition in vivo. J. Neurosci. 2007, 27:627-633.
28. von Heijne G. Membrane-protein topology. Nat. Rev. Mol. Cell Biol. 2006, 7:909-918.
29. Park E., Rapoport T.A. Mechanisms of Sec61/SecY-mediated protein translocation across membranes. Annu. Rev. Biophys. 2012, 41:21-40.
30. Shao S., Hegde R.S. Membrane protein insertion at the endoplasmic reticulum. Annu. Rev. Cell Dev. Biol. 2011, 27:25-56.
31. Lin P.J., Jongsma C.G., Liao S., Johnson A.E. Transmembrane segments of nascent polytopic membrane proteins control cytosol/ER targeting during membrane integration. J. Cell Biol. 2011, 195:41-54.
32. Hedin L.E., Ojemalm K., Bernsel A., Hennerdal A., Illergard K., Enquist K., Kauko A., Cristobal S., von Heijne G., Lerch-Bader M., Nilsson I., Elofsson A. Membrane insertion of marginally hydrophobic transmembrane helices depends on sequence context. J. Mol. Biol. 2010, 396:221-229.
33. Pitonzo D., Skach W.R. Molecular mechanisms of aquaporin biogenesis by the endoplasmic reticulum Sec61 translocon. Biochim. Biophys. Acta 2006, 1758:976-988.
34. Sadlish H., Skach W.R. Biogenesis of CFTR and other polytopic membrane proteins: new roles for the ribosome-translocon complex. J. Membr. Biol. 2004, 202:115-126.
35. Hessa T., Kim H., Bihlmaier K., Lundin C., Boekel J., Andersson H., Nilsson I., White S.H., von Heijne G. Recognition of transmembrane helices by the endoplasmic reticulum translocon. Nature 2005, 433:377-381.
36. Lundin C., Kim H., Nilsson I., White S.H., von Heijne G. Molecular code for protein insertion in the endoplasmic reticulum membrane is similar for N(in)-C(out) and N(out)-C(in) transmembrane helices. Proc. Natl. Acad. Sci. U.S.A. 2008, 105:15702-15707.
37. Perez-Tur J., Froelich S., Prihar G., Crook R., Baker M., Duff K., Wragg M., Busfield F., Lendon C., Clark R.F., et al. A mutation in Alzheimer's disease destroying a splice acceptor site in the presenilin-1 gene. Neuroreport 1995, 7:297-301.
38. Karlstrom H., Bergman A., Lendahl U., Naslund J., Lundkvist J. A sensitive and quantitative assay for measuring cleavage of presenilin substrates. J. Biol. Chem. 2002, 277:6763-6766.
39. Berezovska O., Lleo A., Herl L.D., Frosch M.P., Stern E.A., Bacskai B.J., Hyman B.T. Familial Alzheimer's disease presenilin 1 mutations cause alterations in the conformation of presenilin and interactions with amyloid precursor protein. J. Neurosci. 2005, 25:3009-3017.
40. Kornilova A.Y., Bihel F., Das C., Wolfe M.S. The initial substrate-binding site of gamma-secretase is located on presenilin near the active site. Proc. Natl. Acad. Sci. U.S.A. 2005, 102:3230-3235.
41. Hessa T., Meindl-Beinker N.M., Bernsel A., Kim H., Sato Y., Lerch-Bader M., Nilsson I., White S.H., von Heijne G. Molecular code for transmembrane-helix recognition by the Sec61 translocon. Nature 2007, 450:1026-1030.
42. Enquist K., Fransson M., Boekel C., Bengtsson I., Geiger K., Lang L., Pettersson A., Johansson S., von Heijne G., Nilsson I. Membrane-integration characteristics of two ABC transporters, CFTR and P-glycoprotein. J. Mol. Biol. 2009, 387:1153-1164.
43. Johansson M., Nilsson I., von Heijne G. Positively charged amino acids placed next to a signal sequence block protein translocation more efficiently in Escherichia coli than in mammalian microsomes. Mol. Gen. Genet. 1993, 239:251-256.
44. Nilsson I., Johnson A.E., von Heijne G. Cleavage of a tail-anchored protein by signal peptidase. FEBS Lett. 2002, 516:106-108.
45. Fukumori A., Fluhrer R., Steiner H., Haass C. Three-amino acid spacing of presenilin endoproteolysis suggests a general stepwise cleavage of gamma-secretase-mediated intramembrane proteolysis. J. Neurosci. 2010, 30:7853-7862.
46. Knappenberger K.S., Tian G., Ye X., Sobotka-Briner C., Ghanekar S.V., Greenberg B.D., Scott C.W. Mechanism of gamma-secretase cleavage activation: is gamma-secretase regulated through autoinhibition involving the presenilin-1 exon 9 loop?. Biochemistry 2004, 43:6208-6218.
47. Kauko A., Hedin L.E., Thebaud E., Cristobal S., Elofsson A., von Heijne G. Repositioning of transmembrane alpha-helices during membrane protein folding. J. Mol. Biol. 2010, 397:190-201.
48. Sadlish H., Pitonzo D., Johnson A.E., Skach W.R. Sequential triage of transmembrane segments by Sec61alpha during biogenesis of a native multispanning membrane protein. Nat. Struct. Mol. Biol. 2005, 12:870-878.
49. Sato C., Morohashi Y., Tomita T., Iwatsubo T. Structure of the catalytic pore of gamma-secretase probed by the accessibility of substituted cysteines. J. Neurosci. 2006, 26:12081-12088.
50. Sobhanifar S., Schneider B., Lohr F., Gottstein D., Ikeya T., Mlynarczyk K., Pulawski W., Ghoshdastider U., Kolinski M., Filipek S., Guntert P., Bernhard F., Dotsch V. Structural investigation of the C-terminal catalytic fragment of presenilin 1. Proc. Natl. Acad. Sci. U.S.A. 2010, 107:9644-9649.
51. Nilsson I.M., von Heijne G. Determination of the distance between the oligosaccharyltransferase active site and the endoplasmic reticulum membrane. J. Biol. Chem. 1993, 268:5798-5801.
52. Stefansson A., Armulik A., Nilsson I., von Heijne G., Johansson S. Determination of N- and C-terminal borders of the transmembrane domain of integrin subunits. J. Biol. Chem. 2004, 279:21200-21205.
53. Nilsson I., Saaf A., Whitley P., Gafvelin G., Waller C., von Heijne G. Proline-induced disruption of a transmembrane alpha-helix in its natural environment. J. Mol. Biol. 1998, 284:1165-1175.
54. Teranishi Y., Hur J.Y., Welander H., Franberg J., Aoki M., Winblad B., Frykman S., Tjernberg L.O. Affinity pulldown of gamma-secretase and associated proteins from human and rat brain. J. Cell. Mol. Med. 2009.
55. Okochi M., Tagami S., Yanagida K., Takami M., Kodama T.S., Mori K., Nakayama T., Ihara Y., Takeda M. Gamma-secretase modulators and presenilin 1 mutants act differently on presenilin/gamma-secretase function to cleave Abeta42 and Abeta43. Cell Rep. 2013, 3:42-51.
56. Olsson F., Schmidt S., Althoff V., Munter L.M., Jin S., Rosqvist S., Lendahl U., Multhaup G., Lundkvist J. Characterization of intermediate steps in amyloid beta (Abeta) production under near-native conditions. J. Biol. Chem. 2013, 289:1540-1550.
57. Dimitrov M., Alattia J.R., Lemmin T., Lehal R., Fligier A., Houacine J., Hussain I., Radtke F., Dal Peraro M., Beher D., Fraering P.C. Alzheimer's disease mutations in APP but not gamma-secretase modulators affect epsilon-cleavage-dependent AICD production. Nat. Commun. 2013, 4:2246.
58. Li X., Dang S., Yan C., Gong X., Wang J., Shi Y. Structure of a presenilin family intramembrane aspartate protease. Nature 2013, 493:56-61.
59. Wolfe M.S., Kopan R. Intramembrane proteolysis: theme and variations. Science 2004, 305:1119-1123.
60. Wang Y., Zhang Y., Ha Y. Crystal structure of a rhomboid family intramembrane protease. Nature 2006, 444:179-180.
61. Mathews P.M., Cataldo A.M., Kao B.H., Rudnicki A.G., Qin X., Yang J.L., Jiang Y., Picciano M., Hulette C., Lippa C.F., Bird T.D., Nochlin D., Walter J., Haass C., Levesque L., Fraser P.E., Andreadis A., Nixon R.A. Brain expression of presenilins in sporadic and early-onset, familial Alzheimer's disease. Mol. Med. 2000, 6:878-891.
62. Laudon H., Mathews P.M., Karlstrom H., Bergman A., Farmery M.R., Nixon R.A., Winblad B., Gandy S.E., Lendahl U., Lundkvist J., Naslund J. Co-expressed presenilin 1 NTF and CTF form functional gamma-secretase complexes in cells devoid of full-length protein. J. Neurochem. 2004, 89:44-53.
63. Taniguchi Y., Karlstrom H., Lundkvist J., Mizutani T., Otaka A., Vestling M., Bernstein A., Donoviel D., Lendahl U., Honjo T. Notch receptor cleavage depends on but is not directly executed by presenilins. Proc. Natl. Acad. Sci. U.S.A. 2002, 99:4014-4019.
64. Donoviel D.B., Hadjantonakis A.K., Ikeda M., Zheng H., Hyslop P.S., Bernstein A. Mice lacking both presenilin genes exhibit early embryonic patterning defects. Genes Dev. 1999, 13:2801-2810.
65. Wanngren J., Franberg J., Svensson A.I., Laudon H., Olsson F., Winblad B., Liu F., Naslund J., Lundkvist J., Karlstrom H. The large hydrophilic loop of presenilin 1 is important for regulating gamma-secretase complex assembly and dictating the amyloid beta peptide (Abeta) Profile without affecting Notch processing. J. Biol. Chem. 2010, 285:8527-8536.
66. Pamren A., Wanngren J., Tjernberg L.O., Winblad B., Bhat R., Naslund J., Karlstrom H. Mutations in nicastrin protein differentially affect amyloid beta-peptide production and Notch protein processing. J. Biol. Chem. 2011, 286:31153-31158.
67. Hashimoto M., Bogdanovic N., Volkmann I., Aoki M., Winblad B., Tjernberg L.O. Analysis of microdissected human neurons by a sensitive ELISA reveals a correlation between elevated intracellular concentrations of Abeta42 and Alzheimer's disease neuropathology. Acta Neuropathol. 2010, 119:543-554.
68. Walter P., Blobel G. Preparation of microsomal membranes for cotranslational protein translocation. Methods Enzymol. 1983, 96:84-93.
69. Franberg J., Svensson A.I., Winblad B., Karlstrom H., Frykman S. Minor contribution of presenilin 2 for gamma-secretase activity in mouse embryonic fibroblasts and adult mouse brain. Biochem. Biophys. Res. Commun. 2011, 404:564-568.
70. Raux G., Guyant-Marechal L., Martin C., Bou J., Penet C., Brice A., Hannequin D., Frebourg T., Campion D. Molecular diagnosis of autosomal dominant early onset Alzheimer's disease: an update. J. Med. Genet. 2005, 42:793-795.
71. Campion D., Dumanchin C., Hannequin D., Dubois B., Belliard S., Puel M., Thomas-Anterion C., Michon A., Martin C., Charbonnier F., Raux G., Camuzat A., Penet C., Mesnage V., Martinez M., Clerget-Darpoux F., Brice A., Frebourg T. Early-onset autosomal dominant Alzheimer disease: prevalence, genetic heterogeneity, and mutation spectrum. Am. J. Hum. Genet. 1999, 65:664-670.