Notch and presenilins in vertebrates and invertebrates: Implications for neuronal development and degeneration

Current Opinion in Neurobiology

Volumn 10, Issue 1, 2000, Pages 50-57

  Selkoe, Dennis J ^a  

^a HARVARD MEDICAL SCHOOL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AMYLOID BETA PROTEIN; AMYLOID PRECURSOR PROTEIN; CELL SURFACE RECEPTOR; ENZYME INHIBITOR; GAMMA SECRETASE; NOTCH RECEPTOR; PRESENILIN 1; PRESENILIN 2;

ALZHEIMER DISEASE; CELL ACTIVATION; CELL FATE; CELL NUCLEUS; DRUG PROTEIN BINDING; ENZYME INHIBITOR COMPLEX; FLY; GENETIC REGULATION; HUMAN; INVERTEBRATE; NERVE CELL DEGENERATION; NERVE CELL DIFFERENTIATION; NONHUMAN; PRIORITY JOURNAL; PROTEIN DEGRADATION; PROTEIN DOMAIN; REVIEW; SIGNAL TRANSDUCTION; VERTEBRATE; WORM;

EID: 0033966452     PISSN: 09594388     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0959-4388(99)00054-9     Document Type: Review

References (59)

1. Kimble J., Simpson P. The LIN-12/Notch signaling pathway and its regulation. Annu Rev Cell Dev Biol. 13:1997;333-361.
2. Greenwald I. LIN-12/Notch signaling: lessons from worms and flies. Genes Dev. 12:1998;1751-1762.
3. Artavanis-Tsakonas S., Rand M.D., Lake R.J. Notch signaling: cell fate control and signal integration in development. Science. 284:1999;770-776.
4. Kimble J.E., White J.G. On the control of germ cell development in Caenorhabditis elegans. Dev Biol. 81:1981;208-219.
5. Doherty D., Feger G., Younger-Shepherd S., Jan L.Y., Jan Y.N. Delta is a ventral to dorsal signal complementary to Serrate, another Notch ligand, in Drosophila wing formation. Genes Dev. 10:1996;421-434.
6. Kopan R., Schroeter E.H., Weintraub H., Nye J.S. Signal transduction by activated mNotch: importance of proteolytic processing and its regulation by the extracellular domain. Proc Natl Acad Sci USA. 93:1996;1683-1688.
7. Schroeter E.H., Kisslinger J.A., Kopan R. Notch-1 signalling requires ligand-induced proteolytic release of intracellular domain. Nature. 393:1998;382-386. Mutation of a crucial valine in the TM domain of murine Notch-1 prevents proteolytic release of NICD to the nucleus, thereby blocking signaling. Tiny amounts of nuclear NICD are apparently sufficient for signaling. Ligand binding (by Jagged-1) induces release of NICD from full-length Notch-1 and NICD nuclear entry.
8. •]. Furthermore, NICD and particularly its CDC10 repeats can activate transcription of target genes.
9. •] show that Delta-dependent proteolysis of full-length Notch precedes and is needed for transcriptional activation by Notch in Drosophila.
10. •] show that Delta-dependent proteolysis of Notch precedes and is needed for transcriptional activation by NICD in Drosophila; moreover, complexing of NICD with Su(H) in the cytoplasm and on membranes may regulate nuclear entry of NICD.
11. 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 γ-secretase activity. Nature. 398:1999;513-517. Mutations of two conserved aspartates found in TM6 and TM7 of all presenilins prevents presenilin endoproteolysis between TM6 and TM7 and sharply reduces the γ-secretase cleavage of the APP carboxy-terminal fragment C99 to release Aβ. The results suggest that PS is either an essential 'diaspartyl' cofactor for γ-secretase or is itself γ-secretase, a unique intramembranous aspartyl protease.
12. De Strooper B., Annaert W., Cupers P., Saftig P., Craessaerts K., Mumm J.S., Schroeter E.H., Schrijvers V., Wolfe M.S., Ray W.J., Goate A.et al. A presenilin-1-dependent γ-secretase-like protease mediates release of Notch intracellular domain. Nature. 398:1999;518-522. In neurons of mice with PS1 deletions, the maturation of Notch by a furin-cleavage within the Golgi is unperturbed but the subsequent intramembranous cleavage of mature Notch to release NICD is blocked; moreover, seven inhibitors that block the γ-secretase cleavage of APP likewise block the analogous step in Notch processing, closely linking these protease activities.
13. Struhl G., Greenwald I. Presenilin is required for activity and nuclear access of Notch in Drosophila. Nature. 398:1999;522-525. The effects of null mutations of the Drosophila gene encoding presenilin are essentially indistinguishable from those of null mutations in the gene encoding Notch, and this is because presenilin is absolutely required for the final intramembranous cleavage of Notch that releases NICD to the nucleus.
14. ••], these authors suggest that PS acts upstream of both the ectodomain and intramembranous cleavages of Notch.
15. Sherrington R., Rogaev E.I., Liang Y., Rogaeva E.A., Levesque G., Ikeda M., Chi H., Lin C., Li G., Holman K.et al. Cloning of a novel gene bearing missense mutations in early onset familial Alzheimer's disease. Nature. 375:1995;754-760.
16. Levy-Lahad E., Wasco W., Poorkaj P., Romano D.M., Oshima J., Pettingell H., Yu C., Jondro P.D., Schmidt S.D., Wang K.et al. Candidate gene for the chromosome 1 familial Alzheimer's disease locus. Science. 269:1995;973-977.
17. Levitan D., Greenwald I. Facilitation of lin-12-mediated signalling by sel-12, a Caenorhabditis elegans S182 Alzheimer's disease gene. Nature. 377:1995;351-354.
18. Selkoe D.J. Translating cell biology into therapeutic advances in Alzheimer's disease. Nature. 399:1999;A23-A31.
19. Wolfe M.S., Xia W., Moore C.L., Leatherwood D.D., Ostaszewski B.L., Rahmati T., Donkor I.O., Selkoe D.J. Peptidomimetic probes and molecular modeling suggest Alzheimer's γ-secretase is an intramembrane-cleaving aspartyl protease. Biochem. 38:1999;4720-4727. Reviews current evidence that γ-secretase is an unusual aspartyl protease that cleaves its membrane-anchored substrates within the phospholipid bilayer.
20. Vassar R., Bennett B.D., Babu-Khan S., Kahn S., Mendiaz E.A., Denis P., Teplow D.B., Ross S., Amarante P., Loeloff R.et al. Beta-secretase cleavage of Alzheimer's amyloid precursor protein by the transmembrane aspartic protease BACE. Science. 286:1999;735-741.
21. Yan R., Bienkowski M.J., Shuck M.E., Miao H., Tory M.C., Pauley A.M., Brashier J.R., Stratman N.C., Mathews W.R., Buhl A.E.et al. Membrane-anchored aspartyl protease with Alzheimer's disease beta-secretase activity. Nature. 402:1999;533-537.
22. Sinha A., Anderson J.P., Barbour R., Basi G.S., Caccavello R., Davis D., Doan M., Dovey H.F., Frigon N., Hong J.et al. Purification and cloning of amyloid precursor beta-secretase from human brain. Nature. 402:1999;537-540.
23. De Strooper B., Saftig P., Craessaerts K., Vanderstichele H., Gundula G., Annaert W., Von Figura K., Van Leuven F. Deficiency of presenilin-1 inhibits the normal cleavage of amyloid precursor protein. Nature. 391:1998;387-390. Original report of the requirement for presenilin in regulating the normal intramembranous cleavage of APP by the proteolytic activity called γ-secretase.
24. Song W., Nadeau P., Yuan M., Yang X., Shen J., Yankner B.A. 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. 96:1999;6959-6963. These authors also find a requirement for PS1 to mediate the proteolytic release of mammalian NICD to the nucleus but make the unexpected observation that AD-causing missense mutations in PS1 actually decrease this release, that is they are loss-of-function mutations in mammalian cells.
25. Qian S., Jiang P., Guan X.M., Singh G., Trumbauer M.E., Yu H., Chen H.Y., Van de Ploeg L.H., Zheng H. Mutant human presenilin 1 protects presenilin 1 null mouse against embryonic lethality and elevates Abeta1-42/43 expression. Neuron. 20:1998;611-617.
26. Davis J.A., Naruse S., Chen H., Eckman C., Younkin S., Price D.L., Borchelt D.R., Sisodia S.S., Wong P.C. An Alzheimer's disease-linked PS1 variant rescues the developmental abnormalities of PS1-deficient embryos. Neuron. 20:1998;603-609.
27. Li X., Greenwald I. Additional evidence for an eight transmembrane-domain topology for Caenorhabditis elegans and human presenilins. Proc Natl Acad Sci USA. 95:1998;7109-7114. Provides new data supporting the existence of eight transmembrane domains, rather than six or seven, in the presenilins and critically discusses earlier findings on this important issue.
28. Thinakaran G., Borchelt D.R., Lee M.K., Slunt H.H., Spitzer L., Kim G., Ratovitsky T., Davenport F., Nordstedt C., Seeger M.et al. Endoproteolysis of presenilin 1 and accumulation of processed derivatives in vivo. Neuron. 17:1996;181-190.
29. Saura C.A., Tomita T., Davenport F., Harris C.L., Iwatsubo T., Thinakaran G. Evidence that intramolecular associations between presenilin domains are obligatory for endoproteolytic processing. J Biol Chem. 274:1999;13818-13823.
30. Steiner H., Capell A., Pesold B., Citron M., Kloetzek P.M., Selkoe D.J., Romig H., Mandla K., Haass C. Expression of Alzheimer's disease-associated presenilin-1 is controlled by proteolytic degradation and complex formation. J Biol Chem. 273:1998;32322-32331.
31. Steiner H., Duff K., Capell A., Romig H., Grim M.G., Lincoln S., Hardy J., Yu X., Picciano M., Fechteler K.et al. A loss of function mutation of presenilin-2 interferes with amyloid β-peptide production and Notch signaling. J Biol Chem. 274:1999;28669-28673.
32. Kimberly W.T., Xia W., Rahmati R., Wolfe M.S., Selkoe D.J. The transmembrane aspartates in presenilin 1 and 2 are obligatory for γ-secretase activity and amyloid β-protein generation. J Biol Chem. 2000;. in press.
33. 42 through stabilization and endoproteolysis of presenilin. J Neurosci. 19:1999;10627-10634. Deletional and mutagenesis studies of PS2 and PS1 reveal that their extreme carboxyl termini are crucial for the proper endoproteolysis, stabilization and function of the presenilins. This raises the spectre that the unknown 'limiting cellular factor(s)' for PS stabilization interact with PS at its carboxyl terminus.
34. 42 overproduction. Soc Neurosci Abstr. 25:1999;56.
35. Weidemann A., Paliga K., Durrwang U., Czech C., Evin G., Masters C.L., Beyreuther K. Formation of stable complexes between two Alzheimer's disease gene products: Presenilin-2 and β-amyloid precursor protein. Nat Med. 3:1997;328-332.
36. Xia W., Zhang J., Perez R., Koo E.H., Selkoe D.J. Interaction between amyloid precursor protein and presenilins in mammalian cells: implications for the pathogenesis of Alzheimer's disease. Proc Natl Acad Sci USA. 94:1997;8208-8213.
37. Ray W.J., Yao M., Nowotny P., Mumm J., Zhang W., Wu J.Y., Kopan R., Goate A.M. Evidence for a physical interaction between presenilin and Notch. Proc Natl Acad Sci USA. 96:1999;3263-3268.
38. Thinakaran G., Regard J.B., Bouton C.M.L., Harris C.L., Price D.L., Borchelt D.R., Sisodia S.S. Stable association of presenilin derivatives and absence of presenilin interactions with APP. Neurobiol Disease. 4:1998;438-453.
39. Naruse S., Thinakaran G., Luo J.J., Kusiak J.W., Tomita T., Iwatsubo T., Qian X., Ginty D.D., Price D.L., Borchelt D.R.et al. Effects of PS1 deficiency on membrane protein trafficking in neurons. Neuron. 21:1998;1213-1221. The authors review their data that presenilin and APP do not interact biochemically and provide evidence for an alternate hypothesis: that the function of PS in APP processing is to regulate the membrane trafficking of APP and other proteins.
40. Ye Y., Fortini M.E. Characterization of Drosophila presenilin and its colocalization with Notch during development. Mech Dev. 79:1998;199-211.
41. Kovacs D.M., Fausett H.J., Page K.J., Kim T-W., Mori R.D., Merriam D.E., Hollister R.D., Hallmark O.G., Mancini R., Felsenstein K.et al. Alzheimer-associated presenilins 1 and 2: neuronal expression in brain and localization to intracellular membranes in mammalian cells. Nat Med. 2:1996;224-229.
42. Annaert W.G., Levesque L., Craessaerts K., Dierinck I., Snellings G., Westaway D., Zhang L., St George-Hyslop P., Cordell B., Fraser P., De Strooper B. Presenilin 1 controls γ-secretase processing of amyloid precursor protein in pre-Golgi compartments of hippocampal neurons. J Cell Biol. 147:1999;277-294.
43. Schwarzman A.L., Singh N., Tsiper M., Gregori L., Dranovsky A., Vitek M.P., Glabe C.G., St George-Hyslop P.H., Goldgaber D. Endogenous presenilin 1 redistributes to the surface of lamellipodia upon adhesion of Jurkat cells to a collagen matrix. Proc Natl Acad Sci USA. 96:1999;7932-7937.
44. Ray W.J., Yao M., Mumm J., Schroeter E.H., deStrooper B., Saftig P., Wolfe M., Selkoe D.J., Kpoan R., Goate A.M. Cell surface presenilin-1 participates in the γ-secretase-like proteolysis of Notch. J Biol Chem. 274:1999;36801-36807. Provides the clearest biochemical evidence to date that some mammalian PS reaches the cell surface, where it can complex with mature Notch, placing it in a locus appropriate for participating in both Notch NICD release and Aβ generation.
45. Perez R.G., Soriano S., Hayes J.D., Ostaszewski B.L., Xia W., Selkoe D.J., Chen X., Stokin G.B., Koo E.H. Mutagenesis identifies new signals for β-amyloid precursor protein endocytosis, turnover and the generation of secreted fragments, including A42. J Biol Chem. 274:1999;18851-18856.
46. Levitan D., Greenwald I. LIN-12 protein expression and localization during vulval development in C. elegans. Development. 125:1998;3101-3109.
47. ••] show that the genes frizzled (fz) and disheveled (dsh) act upstream of Notch in the polarized cell fate of the R3 and R4 photoreceptor cells during ommatidial development in the fly eye. This seems to occur because Fz/Dsh promote activity of the Notch ligand, Delta, thus inhibiting Notch receptor activity in R3 and enhancing it in R4.
48. ••].
49. Lanford P.J., Lan Y., Jiang R., Lindsell C., Weinmaster G., Gridley T., Kelley M.W. Notch signalling pathway mediates hair cell development in mammalian cochlea. Nat Genet. 21:1999;289-292.
50. Matsuno K., Eastman D., Mitsiades T., Quinn A.M., Carcanciu M.L., Ordentlich P., Kadesch T., Artavanis-Tsakonas S. Human deltex is a conserved regulator of Notch signalling. Nat Genet. 19:1998;74-78.
51. Bigas A., Martin D.I., Milner L.A. Notch1 and Notch2 inhibit myeloid differentiation in response to different cytokines. Mol Cell Biol. 18:1998;2324-2333. An example of numerous studies that demonstrate a critical role for Notch signaling in the differentiation of hematopoietic progenitor cells in adult humans. Such findings raise theoretical concerns about potential side effects of inhibiting presenilin function to chronically lower Aβ production in AD.
52. Sestan N., Artavanis-Tsakonas S., Rakic P. Contact-dependent inhibition of cortical neurite growth mediated by notch signaling. Science. 286:1999;741-746. Levels of Notch activity in mammalian neurons correlate closely with the degree of differentiation of those neurons. Low Notch activity allows neurite extension and a mature neuronal phenotype, whereas high activity arrests the neurons' ability to extend and elaborate neurites. This work signifies that, in addition to the role of Notch-mediated lateral signaling in specifying neuronal fate, Notch participates importantly in regulating the length and complexity of axons.
53. Shen J., Bronson R.T., Chen D.F., Xia W., Selkoe D.J., Tonegawa S. Skeletal and CNS defects in presenilin-1 deficient mice. Cell. 89:1997;629-639.
54. Guo Y., Livne-Bar I., Zhou L., Boulianne G.L. Drosophila presenilin is required for neuronal differentiation and affects Notch subcellular localization and signaling. J Neurosci. 19:1999;8435-8442.
55. Wang S., Sdrulla A.D., diSibio G., Bush G., Nofziger D., Hicks C., Weinmaster G., Barres B.A. Notch receptor activation inhibits oligodendrocyte differentiation. Neuron. 21:1998;63-75.
56. Joutel A., Corpechot C., Ducros A., Vahedi K., Chabriat H., Mouton P., Alamowitch S., Domenga V., Cecillion M., Marechal E.et al. Notch3 mutations in CADASIL, a hereditary adult-onset condition causing stroke and dementia. Nature. 383:1996;707-710.
57. Oda T., Elkahloun A.G., Pike B.L., Okajima K., Krantz I.D., Genin A., Piccoli D.A., Meltzer P.S., Spinner N.B., Collins F.S., Chandrasekharappa S.C. Mutations in the human Jagged1 gene are responsible for Alagille syndrome. Nat Genet. 16:1997;235-242.
58. Li L., Krantz I.D., Deng Y., Genin A., Banta A.B., Collins C.C., Qi M., Trask B.J., Kuo W.L., Cochran J.et al. Alagille syndrome is caused by mutations in human Jagged1, which encodes a ligand for Notch1. Nat Genet. 3:1997;243-251.
59. Capobianco A.J., Zagouras P., Blaumueller C.M., Artavanis-Tsakonas S., Bishop J.M. Neoplastic transformation by truncated alleles of human NOTCH1/TAN1 and NOTCH2. Mol Cell Biol. 17:1997;6265-6273.