DNA synthesis and neuronal apoptosis caused by familial Alzheimer disease mutants of the amyloid precursor protein are mediated by the p21 activated kinase PAK3

Journal of Neuroscience

Volumn 23, Issue 17, 2003, Pages 6914-6927

  McPhie, Donna L ^a   Coopersmith, Robert ^e   Hines Peralta, Andrew ^a   Chen, Yuzhi ^a   Ivins, Kathryn J ^a   Manly, Susan P ^b   Kozlowski, Michael R ^c   Neve, Kim A ^d   Neve, Rachael L ^a  

^a MCLEAN HOSPITAL   (United States)

^b Infinity Pharmaceuticals Inc   (United States)

^c Fifth Day Therapeutics Inc   (United States)

^d OREGON HEALTH AND SCIENCE UNIVERSITY   (United States)

^e MILLENNIUM PHARMACEUTICALS INC   (United States)

Author keywords

Alzheimer disease; Amyloid precursor protein; Apoptosis; APP intracellular domain; Cell cycle; Heterotrimeric G proteins; P21 activated kinase

Indexed keywords

AMYLOID PRECURSOR PROTEIN; CELL DNA; GUANINE NUCLEOTIDE BINDING PROTEIN; P21 ACTIVATED KINASE; PERTUSSIS TOXIN; PROTEIN P21; PROTEIN SERINE THREONINE KINASE; UNCLASSIFIED DRUG;

ALZHEIMER DISEASE; ANIMAL CELL; APOPTOSIS; ARTICLE; BRAIN NERVE CELL; CELL CYCLE; CELL CYCLE G0 PHASE; CELL CYCLE G1 PHASE; CONTROLLED STUDY; DNA SYNTHESIS; ENZYME ACTIVATION; ENZYME MECHANISM; FAMILIAL DISEASE; GENE MUTATION; NERVE CELL CULTURE; NERVE CELL NECROSIS; NONHUMAN; PRIORITY JOURNAL; PROTEIN BINDING; PROTEIN DOMAIN; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN PROTEIN INTERACTION; RAT; SIGNAL TRANSDUCTION;

EID: 0043135185     PISSN: 02706474     EISSN: None     Source Type: Journal    
DOI: 10.1523/jneurosci.23-17-06914.2003     Document Type: Article

References (59)

1. Arendt T (2002) Dysregulation of neuronal differentiation and cell cycle control in Alzheimer's disease. J Neural Transm Suppl 62:77-85.
2. Arendt T, Rodel L, Gartner U, Holzer M (1996) Expression of the cyclin-dependent kinase inhibitor p16 in Alzheimer's disease. NeuroReport 7:3047-3049.
3. cd42/rac activated kinase. J Biol Chem 270:22731-22737.
4. o heterotrimeric protein within a cell compartment specialized in signal transduction. J Neurosci 19:1717-1727.
5. Burbelo PD, Brechsel D, Hall A (1995) A conserved binding motif defines numerous candidate target proteins for both Cdc42 and Rac GTPases. J Biol Chem 270:29071-29074.
6. Bursztajn S, DeSouza R, McPhie DL, Berman SA, Shioi J, Robakis NK, Neve RL (1998) Overexpression in neurons of human presenilin-1 or a presenilin-1 familial Alzheimer disease mutant does not enhance apoptosis. J Neurosci 18:9790-9799.
7. Busser J, Geldmacher DS, Herrup K (1998) Ectopic cell cycle proteins predict the sites of neuronal cell death in Alzheimer's disease brain. J Neurosci 18:2801-2807.
8. Buxbaum J, Thinakaran G, Koliatsos V, O'Callahan J, Slunt HH, Price DL, Sisodia SS (1990) Processing of Alzheimer β/A4 amyloid precursor protein: Modulation by agents that regulate protein phosphorylation. Proc Natl Acad Sci USA 87:6003-6006.
9. Cao X, Südhof TC (2001) A transcriptionally active complex of APP with Fe65 and histone acetyltransferase Tip60. Science 293:115-120.
10. Chen Y, McPhie DL, Hirschberg J, Neve RL (2000) The amyloid precursor protein-binding protein APP-BP1 drives the cell cycle through the S-M checkpoint and causes apoptosis in neurons. J Biol Chem 275:8929-8935.
11. Chow N, Korenberg JR, Chen XN, Neve RL (1996) APP-BP1, a novel protein that binds to the carboxyl-terminal region of the amyloid precursor protein. J Biol Chem 271:11339-11346.
12. Chow N, Cox C, Callahan LM, Weimer JM, Guo L, Coleman PD (1998) Expression profiles of multiple genes in single neurons of Alzheimer's disease. Proc Natl Acad Sci USA 95:9620-9625.
13. Copani A, Uberti D, Sortino MA, Bruno V, Nicoletti F, Merno M (2001) Activation of cell-cycle-associated proteins in neuronal death: a mandatory or dispensable path? Trends Neurosci 24:25-31.
14. Cotman CW (1998) Apoptosis decision cascades and neuronal degeneration in Alzheimer's disease. Neurobiol Aging 19:S29-S32.
15. Cotman CW, Anderson AJ (1995) A potential role for apoptosis in neurodegeneration and Alzheimer's disease. Mol Neurobiol 10:19-45.
16. Farinelli SE, Greene LA (1996) Cell cycle blockers mimosine, ciclopirox, and deferoxamine prevent the death of PC12 cells and postmitotic sympathetic neurons after the removal of trophic support. J Neurosci 16:1150-1162.
17. Giambarella U, Yamatsuji T, Okamoto T, Matsui T, Ikezu T, Murayama Y, Levine MA, Katz A, Gautam N, Nishimoto I (1997) G-protein βγ complex-mediated apoptosis by familial Alzheimer's disease mutant of APP. EMBO J 16:4897-4907.
18. Guo Q, Fu W, Xie J, Luo H, Sells SF, Geddes JW, Bondada V, Rangnekar VM, Mattson MP (1998) Par-4 is a mediator of neuronal degeneration associated with the pathogenesis of Alzheimer disease. Nature 4:957-962.
19. Jaffer ZM, Chernoff J (2002) p21-activated kinases: three more join the Pak. Int J Biochem Biol 34:713-717.
20. Jakobi R, Chen CJ, Tuazon PT, Traugh JA (1996) Molecular cloning and sequencing of the cytostatic G-protein-activated protein kinase PAK I. J Biol Chem 271:6206-6211.
21. Joneson T, McDonough M, Bar-Sagi D, Van Aelst L (1998) Kinase suppressor of Ras inhibits the activation of extracellular ligand-regulated (ERK) mitogen-activated protein (MAP) kinase by growth factors, activated Ras, and Ras effectors. J Biol Chem 273:7743-7749.
22. Kinoshita A, Whelan CM, Berezovska O, Hyman BT (2002) The γ-secretase-generated carboxyl-terminal domain of the amyloid precursor protein induces apoptosis via Tip60 in H4 cells. J Biol Chem 277:28530-28536.
23. Kondratick CM, Vandre DD (1996) Alzheimer's disease neurofibrillary tangles contain mitosis-specific phosphoepitopes. J Neurochem 67:2405-2416.
24. Kozlowski MR, Spanoyannis AF, Manly SP, Fidel SA, Neve RL (1992) The neurotoxic carboxy terminal fragment of the Alzheimer amyloid precursor binds specifically to a neuronal cell surface molecule: pH dependence of the neurotoxicity and the binding. J Neurosci 12:1679-1687.
25. Lang J, Nishimoto I, Okamoto T, Regazzi R, Kiraly C, Weller U, Wollheim CB (1995) Direct control of exocytosis by receptor-mediated activation of the heterotrimeric GTPases Gi and G(o) or by the expression of their active G alpha subunits. EMBO J 14:3635-3644.
26. Leberer E, Dignard D, Harcus D, Thomas DY, Whiteway M (1992) The protein kinase homologue Ste20p is required to link the yeast pheromone response G-protein βγ subunits to downstream signalling components. EMBO J 11:4815-4824.
27. Leeuw T, Wu C, Schrag JD, Whiteway M, Thomas DY, Leberer E (1998) Interaction of a G-protein β-subunit with a conserved sequence in Ste20/PAK family protein kinases. Nature 391:191-196.
28. Liu WK, Williams R, Hall F, Dickson D, Yen SH (1995) Detection of a cdc2-related kinase associated with Alzheimer paired helical filaments. Am J Pathol 146:228-238.
29. Manser E, Chong C, Zhao ZS, Leung T, Michael G, Hall C, Lim L (1995) Molecular cloning of a new member of the p21-Cdc42/Rac-activated kinase (PAK) family. J Biol Chem 270:25070-25078.
30. Manser E, Huang HY, Loo TH, Chen XQ, Dong JM, Leung T, Lim L (1997) Expression of constitutively active α-PAK reveals effects of the kinase on actin and focal complexes. Mol Cell Biol 17:1129-1143.
31. Martin GA, Bollag G, McCormick FA, Abo A (1995) A novel serine kinase activated by rac/Cdc42Hs-dependent autophosphorylation is related to PAK65 and Ste20. EMBO J 14:1970-1978.
32. McPhie DL, Lee RKK, Eckman CB, Olstein DH, Durham SP, Yager D, Younkin SG, Wurtman RJ, Neve RL (1997) Neuronal expression of β-amyloid precursor protein Alzheimer mutations causes intracellular accumulation of a C-terminal fragment containing both the amyloid β and cytoplasmic domains. J Biol Chem 272:24743-24746.
33. McPhie DL, Golde T, Eckman CB, Yager D, Younkin SG, Neve RL (2001) The β-secretase cleavage product of the amyloid precursor protein mediates neuronal apoptosis caused by familial Alzheimer's disease mutations. Mol Brain Res 97:103-113.
34. McShea A, Harris PL, Webster KR, Wahl AF, Smith MA (1997) Abnormal expression of the cell cycle regulators P16 and CDK4 in Alzheimer's disease. Am J Pathol 150:1933-1939.
35. Neve RL, Perrone-Bizzozero NI, Finklestein S, Zwiers H, Bird E, Kurnit DM, Benowitz LI (1987) The neuronal growth-associated protein GAP-43 (B-50, F1): Neuronal specificity, developmental regulation and regional expression of the human and rat cDNAs. Mol Brain Res 2:177-183.
36. Nishimoto I, Okamoto T, Matsuura Y, Okamoto T, Murayama Y, Ogata E (1993) Alzheimer amyloid protein precursor complexes with brain GTP-binding protein G(o). Nature 362:75-79.
37. Nishimura I, Uetsuki T, Dani SU, Ohsawa Y, Saito I, Okamura H, Uchiyama Y, Yoshikawa K (1998) Degeneration in vivo of rat hippocampal neurons by wild-type Alzheimer amyloid precursor protein overexpressed by adenovirus-mediated gene transfer. J Neurosci 18:2387-2398.
38. Okamoto T, Takeda S, Murayama Y, Ogata E, Nishimoto I (1995) Ligand-dependent G-protein coupling function of amyloid transmembrane precursor. J Biol Chem 270:4205-4208.
39. Patrick GN, Zukerberg L, Nikolic M, de la Monte S, Dikkes P, Tsai L-H (1999) Conversion of p35 to p25 deregulates Cdk5 activity and promotes neurodegeneration. Nature 402:615-622.
40. Raina AK, Hochman A, Ickes H, Zhu X, Ogawa O, Cash AD, Shimohama S, Perry G, Smith MA (2003) Apoptotic promoters and inhibitors in Alzheimer's disease: who wins out? Prog Neuropsychopharmacol Biol Psychiatry 27:251-254.
41. Ramer SW, Davis RW (1993) A dominant truncation allele identifies a gene, STE20, that encodes a putative protein kinase necessary for mating in Saccharomyces cerevisiae. Proc Natl Acad Sci USA 90:452-456.
42. Ren M, Xu G, Zeng, De Lemos-Chiarandini C, Adesnik M, Sabatini DD (1998) Hydrolysis of GTP on rab11 is required for the direct delivery of transferrin from the pericentriolar recycling compartment to the cell surface but not from sorting endosomes. Proc Natl Acad Sci USA 95:6187-6192.
43. Rohn TT, Ivins KJ, Bahr BA, Cotman CW, Cribbs DH (2000) A monoclonal antibody to amyloid precursor protein induces neuronal apoptosis. J Neurochem 75:2331-2342.
44. Roth KA (2001) Caspases, apoptosis, and Alzheimer disease: causation, correlation, and confusion. J Neuropathol Exp Neurol 60:829-838.
45. Russo T, Faraonio R, Minopoli G, De Candia P, De Renzis S, Zambrano N (1998) Fe65 and the protein network centered around the cytosolic domain of the Alzheimer's β-amyloid precursor protein. FEBS Lett 434:1-7.
46. 2-terminal kinase (JNK) interacting protein 1 (JIP 1) binds the cytoplasmic domain of the Alzheimer's β-amyloid precursor protein (APP). J Biol Chem 277:3767-3775.
47. Seemann J, Weber K, Gerke V (1997) Annexin I targets S100C to early endosomes. FEBS Lett 413:185-190.
48. Sells MA, Knaus UG, Bagrodia S, Ambrose DM, Bokoch GM, Chernoff J (1997) Human p21-activated kinase (Pak1) regulates actin organization in mammalian cells. Curr Biol 7:202-210.
49. Smith TW, Lippa CF (1995) Ki-67 immunoreactivity in Alzheimer's disease and other neurodegenerative disorders. J Neuropathol Exp Neurol 54:297-303.
50. Su JH, Anderson AJ, Cummings BJ, Cotman CW (1994) Immunohistochemical evidence for DNA fragmentation in neurons in the AD brain. NeuroReport 5:2529-2533.
51. Taussig R, Sanchez S, Rifo M, Gilman AG (1992) Inhibition of the ω-conotoxin-sensitive calcium current by distinct G-proteins. Neuron 8:799-809.
52. cdc42/rac1-activated serine/threonine kinase that is rapidly activated by thrombin in platelets. J Biol Chem 270:26690-26697.
53. Ulrich O, Reinsch S, Urbe S, Zerial M, Parton RG (1996) Rab 11 regulates recycling through the pericentriolar recycling endosomes. J Cell Biol 135:913-924.
54. Vincent I, Rosado M, Davies P (1996) Mitotic mechanisms in Alzheimer's disease? J Cell Biol 132:413-425.
55. Vincent I, Jicha G, Rosado M, Dickson D (1997) Aberrant expression of mitotic cdc2/cyclin B1 kinase in degenerating neurons of Alzheimer's disease brain. J Neurosci 17:3588-3598.
56. Vincent I, Zheng JH, Dickson DW, Kress Y, Davies P (1998) Mitotic phosphoepitopes precede paired helical filaments in Alzheimer's disease. Neurobiol Aging 19:287-296.
57. Yamatsuji T, Okamoto T, Takeda S, Fukumoto H, Iwatsubo T, Suzuki N, Asami-Odaka A, Ireland S, Kinane TB, Nishimoto I (1996) G-protein-mediated neuronal DNA fragmentation induced by familial Alzheimer's disease-associated mutants of APP. Science 272:1349-1352.
58. Yang Y, Geldmacher DS, Herrup K (2001) DNA replication precedes neuronal cell death in Alzheimer's disease. J Neurosci 21:2661-2668.
59. Zhao Z-S, Manser E, Chen X-Q, Chong C, Leung T, Lim L (1998) A conserved negative regulatory region in αPAK: inhibition of PAK kinases reveals their morphological roles downstream of cdc42 and rac1. Mol Cell Biol 18:2153-2163.