Two transmembrane aspartates in presenilin-1 required for presenilin endoproteolysis and γ-secretase activity

Nature

Volumn 398, Issue 6727, 1999, Pages 513-517

  Wolfe, Michael S ^a,b   Xia, Weiming ^a   Ostaszewski, Beth L ^a   Diehl, Thekla S ^a   Kimberly, W Taylor ^a   Selkoe, Dennis J ^a  

^a Brigham and Women's Hospital Center for Neurologic Diseases   (United States)

^b UNIVERSITY OF TENNESSEE HEALTH SCIENCE CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AMYLOID BETA PROTEIN; GAMMA SECRETASE; MEMBRANE PROTEIN; PRESENILIN 1; UNCLASSIFIED DRUG;

ALZHEIMER DISEASE; AMINO ACID SUBSTITUTION; ARTICLE; BRAIN CORTEX; CARBOXY TERMINAL SEQUENCE; ENZYME ACTIVITY; GENE MUTATION; HUMAN; NONHUMAN; PATHOGENESIS; PRIORITY JOURNAL; PROTEIN ANALYSIS; PROTEIN DEGRADATION; PROTEIN EXPRESSION; PROTEIN SYNTHESIS;

ALZHEIMER DISEASE; AMYLOID BETA-PROTEIN; AMYLOID BETA-PROTEIN PRECURSOR; AMYLOID PRECURSOR PROTEIN SECRETASES; ANIMALS; ASPARTIC ACID; ASPARTIC ENDOPEPTIDASES; CELL LINE; CELL MEMBRANE; CELL-FREE SYSTEM; CHO CELLS; COENZYMES; COS CELLS; CRICETINAE; ELECTROCHEMISTRY; ENDOPEPTIDASES; EXONS; HUMANS; MEMBRANE PROTEINS; MICROSOMES; MUTAGENESIS, SITE-DIRECTED; PEPTIDE FRAGMENTS; PRESENILIN-1; PROTEIN FOLDING; RECOMBINANT PROTEINS; TRANSFECTION;

EID: 0033535553     PISSN: 00280836     EISSN: None     Source Type: Journal    
DOI: 10.1038/19077     Document Type: Article

References (30)

1. Selkoe, D. J. Cell biology of the amyloid beta-protein precursor and the mechanism of Alzheimer's disease. Annu. Rev. Cell Biol. 10, 373-403 (1994).
2. Hardy, J. The Alzheimer family of diseases: many etiologies, one pathogenesis? Proc. Natl Acad. Sci. USA 94, 2095-2097 (1997).
3. De Strooper, B. et al. Deficiency of presenilin-1 inhibits the normal cleavage of amyloid precursor protein. Nature 391, 387-390 (1998).
4. Levitan, D. et al. Assessment of normal and mutant human presenilin function in Caenorhabditis elegans. Proc. Natl Acad. Sci. USA 93, 14940-14944 (1996).
5. Haass, C. et al. Amyloid beta-peptide is produced by cultured cells during normal metabolism. Nature 359, 322-325 (1992).
6. Li, X. & Greenwald, I. Additional evidence for an eight-transmembrane-domain topology for Caenorhabditis elegans and human presenilins. Proc. Natl Acad. Sci. USA 95, 7109-7114 (1998).
7. Thinakaran, G. et al. Endoproteolysis of presenilin 1 and accumulation of processed derivatives in vivo. Neuron 17, 181-190 (1996).
8. Podlisny, M. B. et al. Presenilin proteins undergo heterogeneous endoproteolysis between Thr291 and Ala299 and occur as stable N- and C-terminal fragments in normal and Alzheimer brain tissue. Neurobiol. Dis. 3, 325-337 (1997).
9. Capell, A. et al. The proteolytic fragments of the Akheimer's disease-associated presenilin-1 form heterodimers and occur as a 100-150-kDa molecular mass complex. J. Biol. Chem. 273, 3205-3211 (3998).
10. Venter, J. C., Fraser, C. M., Kerlavage, A. R. & Buck, M. A. Molecular biology of adrenergic and muscarinic cholinergic receptors. Biochem. Pharmacol. 38, 1197-1208 (1989).
11. Koo, E. H. & Squazzo, S. L. Evidence that production and release of amyloid beta-protein involves the endocytic pathway. J. Biol. Chem. 269, 17386-17389 (1994).
12. Xia, W. et al. Enhanced production and oligomerization of the 42-residue amyloid beta-protein by Chinese hamster ovary cells stably expressing mutant presenilins. J. Biol. Chem. 272, 7977-7982 (1997).
13. Thinakaran, G. et al. Evidence that levels of presenilins (PS1 and PS2) are coordinately regulated by competition for limiting cellular factors. J. Biol. Chem. 272, 28415-28422 (1997).
14. Wolfe, M. S. et al. A substrate-based difluoroketone selectively inhibits Alzheimer's gamma-secretase activity. J. Med. Chem. 41, 6-9 (1998).
15. Wolfe, M. S. et al. Peptidomimetic probes and molecular modelling suggest that Alzheimer's γ-secretase is an intramembrane-cleaving aspartyl protease. Biochemistry (in the press).
16. Xia, W. et al. Presenilin 1 regulates the processing of β-amyloid precursor protein C-terminal fragments and the generation of amyloid β-protein in endoplasmic reticulum and Golgi. Biochem. 37, 16465-16471 (1998).
17. L'Hernault, S. W. & Arduengo, P. M. Mutation of a putative sperm membrane protein in Caenorhabditis elegans prevents sperm differentiation but not its associated meiotic divisions. J. Cell Biol. 119, 55-68 (1992).
18. Li, X. & Greenwald, I. HOP-I, a Caenorhabditis elegans presenilin, appears to be functionally redundant with SEL-12 presenilin and to facilitate LIN-12 and GLP-1 signaling. Proc. Natl. Acad. Sci. USA 94, 12204-12209 (1997).
19. Brockhaus, M. et al. Caspase-mediated cleavage is not required for the activity of presenilins in amyloidogenesis and NOTCH signaling. Neuroreport 9, 1481-1486 (1998).
20. Shen, J. et al. Skeletal and CNS defects in presenilin-1-deficient mice. Cell 89, 629-639 (1997).
21. Wong, P. C. et al. Presenilin 1 is required for Notch1 and DII1 expression in the paraxial mesoderm. Nature 387, 288-292 (1997).
22. Kovacs, D. M. et al. Alzheimer-associated presenilins 1 and 2: neuronal expression in brain and localization to intracellular membranes in mammalian cells. Nature Med. 2, 224-229 (1996).
23. Hua, X., Nohturfft, A., Goldstein, J. L. & Brown, M. S. Sterol resistance in CHO cells traced to point mutation in SREBP cleavage-activating protein. Cell 87, 415-426 (1996).
24. Rawson, R. B. et al. Complementation cloning of S2P, a gene encoding a putative metalloprotease required for intramembrane cleavage of SREBPs. Mol. Cell 1, 47-57 (1997).
25. Boyartchuk, V. L., Ashhy, M. N. & Rine, J. Modulation of Ras and a-factor function by carboxyl-terminal proteolysis. Science 275, 1796-1800 (1997).
26. Levitan, D. & Greenwald, I. Effects of SEL-12 presenilin on LIN-12 localization and function in Caenorhabditis elegans. Development 125, 3599-3606 (1998).
27. Schroeter, R. H., Kisslinger, J. A. & Kopan, R. Notch-1 signalling requires ligand-induced proteolytic release of intracellular domain. Nature 393, 382-385 (1998).
28. De Strooper, B. et al. A presenilin-1-dependent, γ-secretase-like protease mediates release of Notch intracellular domain. Nature 398, 518-522 (1999).
29. Johnson-Wood, K. et al. Amyloid precursor protein processing and Abeta42 deposition in a transgenic mouse model of Alzheimer disease. Proc. Natl Acad. Sci. USA 94, 1550-1555 (1997).
30. Zhang, J. et al. Subcellular distribution and turnover of presenilins in transfected cells. J. Biol. Chem. 273, 12436-12442 (1998).