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Molecular Neurodegeneration
Published in: Molecular Neurodegeneration 1/2007

Open Access 01-12-2007 | Research article

ApoER2 expression increases Aβ production while decreasing Amyloid Precursor Protein (APP) endocytosis: Possible role in the partitioning of APP into lipid rafts and in the regulation of γ-secretase activity

Authors: Rodrigo A Fuentealba, Maria Ines Barría, Jiyeon Lee, Judy Cam, Claudia Araya, Claudia A Escudero, Nibaldo C Inestrosa, Francisca C Bronfman, Guojun Bu, Maria-Paz Marzolo

Published in: Molecular Neurodegeneration | Issue 1/2007

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Abstract

Background

The generation of the amyloid-β peptide (Aβ) through the proteolytic processing of the amyloid precursor protein (APP) is a central event in the pathogenesis of Alzheimer's disease (AD). Recent studies highlight APP endocytosis and localization to lipid rafts as important events favoring amyloidogenic processing. However, the precise mechanisms underlying these events are poorly understood. ApoER2 is a member of the low density lipoprotein receptor (LDL-R) family exhibiting slow endocytosis rate and a significant association with lipid rafts. Despite the important neurophysiological roles described for ApoER2, little is known regarding how ApoER2 regulates APP trafficking and processing.

Results

Here, we demonstrate that ApoER2 physically interacts and co-localizes with APP. Remarkably, we found that ApoER2 increases cell surface APP levels and APP association with lipid rafts. The increase of cell surface APP requires the presence of ApoER2 cytoplasmic domain and is a result of decreased APP internalization rate. Unexpectedly, ApoER2 expression correlated with a significant increase in Aβ production and reduced levels of APP-CTFs. The increased Aβ production was dependent on the integrity of the NPxY endocytosis motif of ApoER2. We also found that expression of ApoER2 increased APP association with lipid rafts and increased γ-secretase activity, both of which might contribute to increased Aβ production.

Conclusion

These findings show that ApoER2 negatively affects APP internalization. However, ApoER2 expression stimulates Aβ production by shifting the proportion of APP from the non-rafts to the raft membrane domains, thereby promoting β-secretase and γ-secretase mediated amyloidogenic processing and also by incrementing the activity of γ-secretase.
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Literature
1.
Selkoe DJ: Alzheimer's disease: genes, proteins, and therapy. Physiol Rev. 2001, 81 (2): 741-766.PubMed
2.
Howlett DR, Jennings KH, Lee DC, Clark MS, Brown F, Wetzel R, Wood SJ, Camilleri P, Roberts GW: Aggregation state and neurotoxic properties of Alzheimer beta-amyloid peptide. Neurodegeneration. 1995, 4 (1): 23-32. 10.1006/neur.1995.0003.CrossRefPubMed
3.
McGowan E, Pickford F, Kim J, Onstead L, Eriksen J, Yu C, Skipper L, Murphy MP, Beard J, Das P, Jansen K, Delucia M, Lin WL, Dolios G, Wang R, Eckman CB, Dickson DW, Hutton M, Hardy J, Golde T: Abeta42 is essential for parenchymal and vascular amyloid deposition in mice. Neuron. 2005, 47 (2): 191-199. 10.1016/j.neuron.2005.06.030.PubMedCentralCrossRefPubMed
4.
Lambert MP, Barlow AK, Chromy BA, Edwards C, Freed R, Liosatos M, Morgan TE, Rozovsky I, Trommer B, Viola KL, Wals P, Zhang C, Finch CE, Krafft GA, Klein WL: Diffusible, nonfibrillar ligands derived from Abeta1-42 are potent central nervous system neurotoxins. Proc Natl Acad Sci U S A. 1998, 95 (11): 6448-6453. 10.1073/pnas.95.11.6448.PubMedCentralCrossRefPubMed
5.
Lacor PN, Buniel MC, Chang L, Fernandez SJ, Gong Y, Viola KL, Lambert MP, Velasco PT, Bigio EH, Finch CE, Krafft GA, Klein WL: Synaptic targeting by Alzheimer's-related amyloid beta oligomers. J Neurosci. 2004, 24 (45): 10191-10200. 10.1523/JNEUROSCI.3432-04.2004.CrossRefPubMed
6.
Jacobsen JS, Wu CC, Redwine JM, Comery TA, Arias R, Bowlby M, Martone R, Morrison JH, Pangalos MN, Reinhart PH, Bloom FE: Early-onset behavioral and synaptic deficits in a mouse model of Alzheimer's disease. Proc Natl Acad Sci U S A. 2006, 103 (13): 5161-5166. 10.1073/pnas.0600948103.PubMedCentralCrossRefPubMed
7.
Annaert W, De Strooper B: A cell biological perspective on Alzheimer's disease. Annu Rev Cell Dev Biol. 2002, 18: 25-51. 10.1146/annurev.cellbio.18.020402.142302.CrossRefPubMed
8.
Riddell DR, Christie G, Hussain I, Dingwall C: Compartmentalization of beta-secretase (Asp2) into low-buoyant density, noncaveolar lipid rafts. Curr Biol. 2001, 11 (16): 1288-1293. 10.1016/S0960-9822(01)00394-3.CrossRefPubMed
9.
Cordy JM, Hussain I, Dingwall C, Hooper NM, Turner AJ: Exclusively targeting beta-secretase to lipid rafts by GPI-anchor addition up-regulates beta-site processing of the amyloid precursor protein. Proc Natl Acad Sci U S A. 2003, 100 (20): 11735-11740. 10.1073/pnas.1635130100.PubMedCentralCrossRefPubMed
10.
Vetrivel KS, Cheng H, Kim SH, Chen Y, Barnes NY, Parent AT, Sisodia SS, Thinakaran G: Spatial segregation of gamma-secretase and substrates in distinct membrane domains. J Biol Chem. 2005, 280 (27): 25892-25900. 10.1074/jbc.M503570200.PubMedCentralCrossRefPubMed
11.
Vetrivel KS, Cheng H, Lin W, Sakurai T, Li T, Nukina N, Wong PC, Xu H, Thinakaran G: Association of gamma-secretase with lipid rafts in post-Golgi and endosome membranes. J Biol Chem. 2004, 279 (43): 44945-44954. 10.1074/jbc.M407986200.PubMedCentralCrossRefPubMed
12.
Lammich S, Kojro E, Postina R, Gilbert S, Pfeiffer R, Jasionowski M, Haass C, Fahrenholz F: Constitutive and regulated alpha-secretase cleavage of Alzheimer's amyloid precursor protein by a disintegrin metalloprotease. Proc Natl Acad Sci U S A. 1999, 96 (7): 3922-3927. 10.1073/pnas.96.7.3922.PubMedCentralCrossRefPubMed
13.
Kojro E, Gimpl G, Lammich S, Marz W, Fahrenholz F: Low cholesterol stimulates the nonamyloidogenic pathway by its effect on the alpha -secretase ADAM 10. Proc Natl Acad Sci U S A. 2001, 98 (10): 5815-5820. 10.1073/pnas.081612998.PubMedCentralCrossRefPubMed
14.
Kinoshita A, Fukumoto H, Shah T, Whelan CM, Irizarry MC, Hyman BT: Demonstration by FRET of BACE interaction with the amyloid precursor protein at the cell surface and in early endosomes. J Cell Sci. 2003, 116 (Pt 16): 3339-3346. 10.1242/jcs.00643.CrossRefPubMed
15.
Kaether C, Schmitt S, Willem M, Haass C: Amyloid precursor protein and Notch intracellular domains are generated after transport of their precursors to the cell surface. Traffic. 2006, 7 (4): 408-415. 10.1111/j.1600-0854.2006.00396.x.CrossRefPubMed
16.
Koo EH, Squazzo SL, Selkoe DJ, Koo CH: Trafficking of cell-surface amyloid beta-protein precursor. I. Secretion, endocytosis and recycling as detected by labeled monoclonal antibody. J Cell Sci. 1996, 109 ( Pt 5): 991-998.
17.
Yamazaki T, Koo EH, Selkoe DJ: Trafficking of cell-surface amyloid beta-protein precursor. II. Endocytosis, recycling and lysosomal targeting detected by immunolocalization. J Cell Sci. 1996, 109 ( Pt 5): 999-1008.
18.
Koo EH, Squazzo SL: Evidence that production and release of amyloid beta-protein involves the endocytic pathway. J Biol Chem. 1994, 269 (26): 17386-17389.PubMed
19.
Perez RG, Soriano S, Hayes JD, Ostaszewski B, Xia W, Selkoe DJ, Chen X, Stokin GB, Koo EH: Mutagenesis identifies new signals for beta-amyloid precursor protein endocytosis, turnover, and the generation of secreted fragments, including Abeta42. J Biol Chem. 1999, 274 (27): 18851-18856. 10.1074/jbc.274.27.18851.CrossRefPubMed
20.
Chyung JH, Selkoe DJ: Inhibition of receptor-mediated endocytosis demonstrates generation of amyloid beta-protein at the cell surface. J Biol Chem. 2003, 278 (51): 51035-51043. 10.1074/jbc.M304989200.CrossRefPubMed
21.
Ehehalt R, Keller P, Haass C, Thiele C, Simons K: Amyloidogenic processing of the Alzheimer beta-amyloid precursor protein depends on lipid rafts. J Cell Biol. 2003, 160 (1): 113-123. 10.1083/jcb.200207113.PubMedCentralCrossRefPubMed
22.
23.
Schmechel DE, Saunders AM, Strittmatter WJ, Crain BJ, Hulette CM, Joo SH, Pericak-Vance MA, Goldgaber D, Roses AD: Increased amyloid beta-peptide deposition in cerebral cortex as a consequence of apolipoprotein E genotype in late-onset Alzheimer disease. Proc Natl Acad Sci U S A. 1993, 90 (20): 9649-9653. 10.1073/pnas.90.20.9649.PubMedCentralCrossRefPubMed
24.
Strittmatter WJ, Saunders AM, Schmechel D, Pericak-Vance M, Enghild J, Salvesen GS, Roses AD: Apolipoprotein E: high-avidity binding to beta-amyloid and increased frequency of type 4 allele in late-onset familial Alzheimer disease. Proc Natl Acad Sci U S A. 1993, 90 (5): 1977-1981. 10.1073/pnas.90.5.1977.PubMedCentralCrossRefPubMed
25.
Li Y, Marzolo MP, van Kerkhof P, Strous GJ, Bu G: The YXXL motif, but not the two NPXY motifs, serves as the dominant endocytosis signal for low density lipoprotein receptor-related protein. J Biol Chem. 2000, 275 (22): 17187-17194. 10.1074/jbc.M000490200.CrossRefPubMed
26.
Ulery PG, Beers J, Mikhailenko I, Tanzi RE, Rebeck GW, Hyman BT, Strickland DK: Modulation of beta-amyloid precursor protein processing by the low density lipoprotein receptor-related protein (LRP). Evidence that LRP contributes to the pathogenesis of Alzheimer's disease. J Biol Chem. 2000, 275 (10): 7410-7415. 10.1074/jbc.275.10.7410.CrossRefPubMed
27.
Pietrzik CU, Busse T, Merriam DE, Weggen S, Koo EH: The cytoplasmic domain of the LDL receptor-related protein regulates multiple steps in APP processing. Embo J. 2002, 21 (21): 5691-5700. 10.1093/emboj/cdf568.PubMedCentralCrossRefPubMed
28.
Cam JA, Zerbinatti CV, Li Y, Bu G: Rapid endocytosis of the low density lipoprotein receptor-related protein modulates cell surface distribution and processing of the beta-amyloid precursor protein. J Biol Chem. 2005, 280 (15): 15464-15470. 10.1074/jbc.M500613200.CrossRefPubMed
29.
Cam JA, Zerbinatti CV, Knisely JM, Hecimovic S, Li Y, Bu G: The low density lipoprotein receptor-related protein 1B retains beta-amyloid precursor protein at the cell surface and reduces amyloid-beta peptide production. J Biol Chem. 2004, 279 (28): 29639-29646. 10.1074/jbc.M313893200.CrossRefPubMed
30.
Andersen OM, Reiche J, Schmidt V, Gotthardt M, Spoelgen R, Behlke J, von Arnim CA, Breiderhoff T, Jansen P, Wu X, Bales KR, Cappai R, Masters CL, Gliemann J, Mufson EJ, Hyman BT, Paul SM, Nykjaer A, Willnow TE: Neuronal sorting protein-related receptor sorLA/LR11 regulates processing of the amyloid precursor protein. Proc Natl Acad Sci U S A. 2005, 102 (38): 13461-13466. 10.1073/pnas.0503689102.PubMedCentralCrossRefPubMed
31.
Hoe HS, Rebeck GW: Regulation of ApoE receptor proteolysis by ligand binding. Brain Res Mol Brain Res. 2005, 137 (1-2): 31-39. 10.1016/j.molbrainres.2005.02.013.CrossRefPubMed
32.
Hoe HS, Wessner D, Beffert U, Becker AG, Matsuoka Y, Rebeck GW: F-spondin interaction with the apolipoprotein E receptor ApoEr2 affects processing of amyloid precursor protein. Mol Cell Biol. 2005, 25 (21): 9259-9268. 10.1128/MCB.25.21.9259-9268.2005.PubMedCentralCrossRefPubMed
33.
Wolozin B: Cholesterol and the biology of Alzheimer's disease. Neuron. 2004, 41 (1): 7-10. 10.1016/S0896-6273(03)00840-7.CrossRefPubMed
34.
Sjogren M, Mielke M, Gustafson D, Zandi P, Skoog I: Cholesterol and Alzheimer's disease--is there a relation?. Mech Ageing Dev. 2006, 127 (2): 138-147. 10.1016/j.mad.2005.09.020.CrossRefPubMed
35.
Jick H, Zornberg GL, Jick SS, Seshadri S, Drachman DA: Statins and the risk of dementia. Lancet. 2000, 356 (9242): 1627-1631. 10.1016/S0140-6736(00)03155-X.CrossRefPubMed
36.
Wolozin B, Kellman W, Ruosseau P, Celesia GG, Siegel G: Decreased prevalence of Alzheimer disease associated with 3-hydroxy-3-methyglutaryl coenzyme A reductase inhibitors. Arch Neurol. 2000, 57 (10): 1439-1443. 10.1001/archneur.57.10.1439.CrossRefPubMed
37.
Fassbender K, Simons M, Bergmann C, Stroick M, Lutjohann D, Keller P, Runz H, Kuhl S, Bertsch T, von Bergmann K, Hennerici M, Beyreuther K, Hartmann T: Simvastatin strongly reduces levels of Alzheimer's disease beta -amyloid peptides Abeta 42 and Abeta 40 in vitro and in vivo. Proc Natl Acad Sci U S A. 2001, 98 (10): 5856-5861. 10.1073/pnas.081620098.PubMedCentralCrossRefPubMed
38.
Refolo LM, Pappolla MA, LaFrancois J, Malester B, Schmidt SD, Thomas-Bryant T, Tint GS, Wang R, Mercken M, Petanceska SS, Duff KE: A cholesterol-lowering drug reduces beta-amyloid pathology in a transgenic mouse model of Alzheimer's disease. Neurobiol Dis. 2001, 8 (5): 890-899. 10.1006/nbdi.2001.0422.CrossRefPubMed
39.
Ledesma MD, Dotti CG: Amyloid excess in Alzheimer's disease: what is cholesterol to be blamed for?. FEBS Lett. 2006, 580 (23): 5525-5532. 10.1016/j.febslet.2006.06.038.CrossRefPubMed
40.
Kim DH, Iijima H, Goto K, Sakai J, Ishii H, Kim HJ, Suzuki H, Kondo H, Saeki S, Yamamoto T: Human apolipoprotein E receptor 2. A novel lipoprotein receptor of the low density lipoprotein receptor family predominantly expressed in brain. J Biol Chem. 1996, 271 (14): 8373-8380. 10.1074/jbc.271.14.8373.CrossRefPubMed
41.
Cuitino L, Matute R, Retamal C, Bu G, Inestrosa NC, Marzolo MP: ApoER2 is endocytosed by a clathrin-mediated process involving the adaptor protein Dab2 independent of its Rafts' association. Traffic. 2005, 6 (9): 820-838. 10.1111/j.1600-0854.2005.00320.x.CrossRefPubMed
42.
D'Arcangelo G, Homayouni R, Keshvara L, Rice DS, Sheldon M, Curran T: Reelin is a ligand for lipoprotein receptors. Neuron. 1999, 24 (2): 471-479. 10.1016/S0896-6273(00)80860-0.CrossRefPubMed
43.
Hiesberger T, Trommsdorff M, Howell BW, Goffinet A, Mumby MC, Cooper JA, Herz J: Direct binding of Reelin to VLDL receptor and ApoE receptor 2 induces tyrosine phosphorylation of disabled-1 and modulates tau phosphorylation. Neuron. 1999, 24 (2): 481-489. 10.1016/S0896-6273(00)80861-2.CrossRefPubMed
44.
Trommsdorff M, Gotthardt M, Hiesberger T, Shelton J, Stockinger W, Nimpf J, Hammer RE, Richardson JA, Herz J: Reeler/Disabled-like disruption of neuronal migration in knockout mice lacking the VLDL receptor and ApoE receptor 2. Cell. 1999, 97 (6): 689-701. 10.1016/S0092-8674(00)80782-5.CrossRefPubMed
45.
Sinagra M, Verrier D, Frankova D, Korwek KM, Blahos J, Weeber EJ, Manzoni OJ, Chavis P: Reelin, very-low-density lipoprotein receptor, and apolipoprotein E receptor 2 control somatic NMDA receptor composition during hippocampal maturation in vitro. J Neurosci. 2005, 25 (26): 6127-6136. 10.1523/JNEUROSCI.1757-05.2005.CrossRefPubMed
46.
Weeber EJ, Beffert U, Jones C, Christian JM, Forster E, Sweatt JD, Herz J: Reelin and ApoE receptors cooperate to enhance hippocampal synaptic plasticity and learning. J Biol Chem. 2002, 277 (42): 39944-39952. 10.1074/jbc.M205147200.CrossRefPubMed
47.
Beffert U, Weeber EJ, Durudas A, Qiu S, Masiulis I, Sweatt JD, Li WP, Adelmann G, Frotscher M, Hammer RE, Herz J: Modulation of synaptic plasticity and memory by Reelin involves differential splicing of the lipoprotein receptor Apoer2. Neuron. 2005, 47 (4): 567-579. 10.1016/j.neuron.2005.07.007.CrossRefPubMed
48.
Wirths O, Multhaup G, Czech C, Blanchard V, Tremp G, Pradier L, Beyreuther K, Bayer TA: Reelin in plaques of beta-amyloid precursor protein and presenilin-1 double-transgenic mice. Neurosci Lett. 2001, 316 (3): 145-148. 10.1016/S0304-3940(01)02399-0.CrossRefPubMed
49.
Motoi Y, Itaya M, Mori H, Mizuno Y, Iwasaki T, Hattori H, Haga S, Ikeda K: Apolipoprotein E receptor 2 is involved in neuritic plaque formation in APP sw mice. Neurosci Lett. 2004, 368 (2): 144-147. 10.1016/j.neulet.2004.06.081.CrossRefPubMed
50.
Botella-Lopez A, Burgaya F, Gavin R, Garcia-Ayllon MS, Gomez-Tortosa E, Pena-Casanova J, Urena JM, Del Rio JA, Blesa R, Soriano E, Saez-Valero J: Reelin expression and glycosylation patterns are altered in Alzheimer's disease. Proc Natl Acad Sci U S A. 2006, 103 (14): 5573-5578. 10.1073/pnas.0601279103.PubMedCentralCrossRefPubMed
51.
Hoe HS, Magill LA, Guenette S, Fu Z, Vicini S, Rebeck GW: FE65 interaction with the ApoE receptor ApoEr2. J Biol Chem. 2006, 281 (34): 24521-24530. 10.1074/jbc.M600728200.CrossRefPubMed
52.
Zerbinatti CV, Wahrle SE, Kim H, Cam JA, Bales K, Paul SM, Holtzman DM, Bu G: Apolipoprotein E and low density lipoprotein receptor-related protein facilitate intraneuronal Abeta42 accumulation in amyloid model mice. J Biol Chem. 2006, 281 (47): 36180-36186. 10.1074/jbc.M604436200.CrossRefPubMed
53.
Brandes C, Novak S, Stockinger W, Herz J, Schneider WJ, Nimpf J: Avian and murine LR8B and human apolipoprotein E receptor 2: differentially spliced products from corresponding genes. Genomics. 1997, 42 (2): 185-191. 10.1006/geno.1997.4702.CrossRefPubMed
54.
York SJ, Arneson LS, Gregory WT, Dahms NM, Kornfeld S: The rate of internalization of the mannose 6-phosphate/insulin-like growth factor II receptor is enhanced by multivalent ligand binding. J Biol Chem. 1999, 274 (2): 1164-1171. 10.1074/jbc.274.2.1164.CrossRefPubMed
55.
Klausner RD, Van Renswoude J, Ashwell G, Kempf C, Schechter AN, Dean A, Bridges KR: Receptor-mediated endocytosis of transferrin in K562 cells. J Biol Chem. 1983, 258 (8): 4715-4724.PubMed
56.
Simons M, Keller P, De Strooper B, Beyreuther K, Dotti CG, Simons K: Cholesterol depletion inhibits the generation of beta-amyloid in hippocampal neurons. Proc Natl Acad Sci U S A. 1998, 95 (11): 6460-6464. 10.1073/pnas.95.11.6460.PubMedCentralCrossRefPubMed
57.
Dovey HF, John V, Anderson JP, Chen LZ, de Saint Andrieu P, Fang LY, Freedman SB, Folmer B, Goldbach E, Holsztynska EJ, Hu KL, Johnson-Wood KL, Kennedy SL, Kholodenko D, Knops JE, Latimer LH, Lee M, Liao Z, Lieberburg IM, Motter RN, Mutter LC, Nietz J, Quinn KP, Sacchi KL, Seubert PA, Shopp GM, Thorsett ED, Tung JS, Wu J, Yang S, Yin CT, Schenk DB, May PC, Altstiel LD, Bender MH, Boggs LN, Britton TC, Clemens JC, Czilli DL, Dieckman-McGinty DK, Droste JJ, Fuson KS, Gitter BD, Hyslop PA, Johnstone EM, Li WY, Little SP, Mabry TE, Miller FD, Audia JE: Functional gamma-secretase inhibitors reduce beta-amyloid peptide levels in brain. J Neurochem. 2001, 76 (1): 173-181. 10.1046/j.1471-4159.2001.00012.x.CrossRefPubMed
58.
Vetrivel KS, Thinakaran G: Amyloidogenic processing of beta-amyloid precursor protein in intracellular compartments. Neurology. 2006, 66 (2 Suppl 1): S69-73.CrossRefPubMed
59.
Chen F, Yang DS, Petanceska S, Yang A, Tandon A, Yu G, Rozmahel R, Ghiso J, Nishimura M, Zhang DM, Kawarai T, Levesque G, Mills J, Levesque L, Song YQ, Rogaeva E, Westaway D, Mount H, Gandy S, St George-Hyslop P, Fraser PE: Carboxyl-terminal fragments of Alzheimer beta-amyloid precursor protein accumulate in restricted and unpredicted intracellular compartments in presenilin 1-deficient cells. J Biol Chem. 2000, 275 (47): 36794-36802. 10.1074/jbc.M006986200.CrossRefPubMed
60.
Farmery MR, Tjernberg LO, Pursglove SE, Bergman A, Winblad B, Naslund J: Partial purification and characterization of gamma-secretase from post-mortem human brain. J Biol Chem. 2003, 278 (27): 24277-24284. 10.1074/jbc.M211992200.CrossRefPubMed
61.
Zou Z, Chung B, Nguyen T, Mentone S, Thomson B, Biemesderfer D: Linking receptor-mediated endocytosis and cell signaling: evidence for regulated intramembrane proteolysis of megalin in proximal tubule. J Biol Chem. 2004, 279 (33): 34302-34310. 10.1074/jbc.M405608200.CrossRefPubMed
62.
Ni Y, Zhao X, Bao G, Zou L, Teng L, Wang Z, Song M, Xiong J, Bai Y, Pei G: Activation of beta2-adrenergic receptor stimulates gamma-secretase activity and accelerates amyloid plaque formation. Nat Med. 2006, 12 (12): 1390-1396. 10.1038/nm1485.CrossRefPubMed
63.
Urra S, Escudero CA, Ramos P, Lisbona F, Allende E, Covarrubias P, Parraguez JI, Zampieri N, Chao MV, Annaert W, Bronfman FC: TrkA receptor activation by nerve growth factor induces shedding of the p75 neurotrophin receptor followed by endosomal gamma-secretase-mediated release of the p75 intracellular domain. J Biol Chem. 2007, 282 (10): 7606-7615. 10.1074/jbc.M610458200.CrossRefPubMed
64.
Bu G, Cam J, Zerbinatti C: LRP in amyloid-beta production and metabolism. Ann N Y Acad Sci. 2006, 1086: 35-53. 10.1196/annals.1377.005.CrossRefPubMed
65.
Andersen OM, Schmidt V, Spoelgen R, Gliemann J, Behlke J, Galatis D, McKinstry WJ, Parker MW, Masters CL, Hyman BT, Cappai R, Willnow TE: Molecular dissection of the interaction between amyloid precursor protein and its neuronal trafficking receptor SorLA/LR11. Biochemistry. 2006, 45 (8): 2618-2628. 10.1021/bi052120v.CrossRefPubMed
66.
Spoelgen R, von Arnim CA, Thomas AV, Peltan ID, Koker M, Deng A, Irizarry MC, Andersen OM, Willnow TE, Hyman BT: Interaction of the cytosolic domains of sorLA/LR11 with the amyloid precursor protein (APP) and beta-secretase beta-site APP-cleaving enzyme. J Neurosci. 2006, 26 (2): 418-428. 10.1523/JNEUROSCI.3882-05.2006.CrossRefPubMed
67.
Gotthardt M, Trommsdorff M, Nevitt MF, Shelton J, Richardson JA, Stockinger W, Nimpf J, Herz J: Interactions of the low density lipoprotein receptor gene family with cytosolic adaptor and scaffold proteins suggest diverse biological functions in cellular communication and signal transduction. J Biol Chem. 2000, 275 (33): 25616-25624. 10.1074/jbc.M000955200.CrossRefPubMed
68.
Stockinger W, Brandes C, Fasching D, Hermann M, Gotthardt M, Herz J, Schneider WJ, Nimpf J: The reelin receptor ApoER2 recruits JNK-interacting proteins-1 and -2. J Biol Chem. 2000, 275 (33): 25625-25632. 10.1074/jbc.M004119200.CrossRefPubMed
69.
Brandes C, Kahr L, Stockinger W, Hiesberger T, Schneider WJ, Nimpf J: Alternative splicing in the ligand binding domain of mouse ApoE receptor-2 produces receptor variants binding reelin but not alpha 2-macroglobulin. J Biol Chem. 2001, 276 (25): 22160-22169. 10.1074/jbc.M102662200.CrossRefPubMed
70.
Kim DH, Magoori K, Inoue TR, Mao CC, Kim HJ, Suzuki H, Fujita T, Endo Y, Saeki S, Yamamoto TT: Exon/intron organization, chromosome localization, alternative splicing, and transcription units of the human apolipoprotein E receptor 2 gene. J Biol Chem. 1997, 272 (13): 8498-8504. 10.1074/jbc.272.13.8498.CrossRefPubMed
71.
Clatworthy AE, Stockinger W, Christie RH, Schneider WJ, Nimpf J, Hyman BT, Rebeck GW: Expression and alternate splicing of apolipoprotein E receptor 2 in brain. Neuroscience. 1999, 90 (3): 903-911. 10.1016/S0306-4522(98)00489-8.CrossRefPubMed
72.
Sun XM, Soutar AK: Expression in vitro of alternatively spliced variants of the messenger RNA for human apolipoprotein E receptor-2 identified in human tissues by ribonuclease protection assays. Eur J Biochem. 1999, 262 (1): 230-239. 10.1046/j.1432-1327.1999.00394.x.CrossRefPubMed
73.
Carey RM, Balcz BA, Lopez-Coviella I, Slack BE: Inhibition of dynamin-dependent endocytosis increases shedding of the amyloid precursor protein ectodomain and reduces generation of amyloid beta protein. BMC Cell Biol. 2005, 6: 30-10.1186/1471-2121-6-30.PubMedCentralCrossRefPubMed
74.
Kaether C, Lammich S, Edbauer D, Ertl M, Rietdorf J, Capell A, Steiner H, Haass C: Presenilin-1 affects trafficking and processing of betaAPP and is targeted in a complex with nicastrin to the plasma membrane. J Cell Biol. 2002, 158 (3): 551-561. 10.1083/jcb.200201123.PubMedCentralCrossRefPubMed
75.
von Arnim CA, Kinoshita A, Peltan ID, Tangredi MM, Herl L, Lee BM, Spoelgen R, Hshieh TT, Ranganathan S, Battey FD, Liu CX, Bacskai BJ, Sever S, Irizarry MC, Strickland DK, Hyman BT: The low density lipoprotein receptor-related protein (LRP) is a novel beta-secretase (BACE1) substrate. J Biol Chem. 2005, 280 (18): 17777-17785. 10.1074/jbc.M414248200.CrossRefPubMed
76.
Rajendran L, Simons K: Lipid rafts and membrane dynamics. J Cell Sci. 2005, 118 (Pt 6): 1099-1102. 10.1242/jcs.01681.CrossRefPubMed
77.
Huse JT, Pijak DS, Leslie GJ, Lee VM, Doms RW: Maturation and endosomal targeting of beta-site amyloid precursor protein-cleaving enzyme. The Alzheimer's disease beta-secretase. J Biol Chem. 2000, 275 (43): 33729-33737. 10.1074/jbc.M004175200.CrossRefPubMed
78.
Rechards M, Xia W, Oorschot VM, Selkoe DJ, Klumperman J: Presenilin-1 exists in both pre- and post-Golgi compartments and recycles via COPI-coated membranes. Traffic. 2003, 4 (8): 553-565.CrossRefPubMed
79.
He X, Li F, Chang WP, Tang J: GGA proteins mediate the recycling pathway of memapsin 2 (BACE). J Biol Chem. 2005, 280 (12): 11696-11703. 10.1074/jbc.M411296200.CrossRefPubMed
80.
Grimm MO, Grimm HS, Patzold AJ, Zinser EG, Halonen R, Duering M, Tschape JA, De Strooper B, Muller U, Shen J, Hartmann T: Regulation of cholesterol and sphingomyelin metabolism by amyloid-beta and presenilin. Nat Cell Biol. 2005, 7 (11): 1118-1123.CrossRefPubMed
81.
May P, Bock HH, Nimpf J, Herz J: Differential glycosylation regulates processing of lipoprotein receptors by gamma-secretase. J Biol Chem. 2003, 278 (39): 37386-37392. 10.1074/jbc.M305858200.CrossRefPubMed
82.
Banker GA, Cowan WM: Rat hippocampal neurons in dispersed cell culture. Brain Res. 1977, 126 (3): 397-342. 10.1016/0006-8993(77)90594-7.CrossRefPubMed
83.
Bottenstein JE, Sato GH: Growth of a rat neuroblastoma cell line in serum-free supplemented medium. Proc Natl Acad Sci U S A. 1979, 76 (1): 514-517. 10.1073/pnas.76.1.514.PubMedCentralCrossRefPubMed
84.
Rosso S, Bollati F, Bisbal M, Peretti D, Sumi T, Nakamura T, Quiroga S, Ferreira A, Caceres A: LIMK1 regulates Golgi dynamics, traffic of Golgi-derived vesicles, and process extension in primary cultured neurons. Mol Biol Cell. 2004, 15 (7): 3433-3449. 10.1091/mbc.E03-05-0328.PubMedCentralCrossRefPubMed
85.
Bali PK, Harris WR: Site-specific rate constants for iron removal from diferric transferrin by nitrilotris(methylenephosphonic acid) and pyrophosphate. Arch Biochem Biophys. 1990, 281 (2): 251-256. 10.1016/0003-9861(90)90440-A.CrossRefPubMed
86.
Annaert WG, Esselens C, Baert V, Boeve C, Snellings G, Cupers P, Craessaerts K, De Strooper B: Interaction with telencephalin and the amyloid precursor protein predicts a ring structure for presenilins. Neuron. 2001, 32 (4): 579-589. 10.1016/S0896-6273(01)00512-8.CrossRefPubMed
87.
Wessel D, Flugge UI: A method for the quantitative recovery of protein in dilute solution in the presence of detergents and lipids. Anal Biochem. 1984, 138 (1): 141-143. 10.1016/0003-2697(84)90782-6.CrossRefPubMed
Metadata
Title
ApoER2 expression increases Aβ production while decreasing Amyloid Precursor Protein (APP) endocytosis: Possible role in the partitioning of APP into lipid rafts and in the regulation of γ-secretase activity
Authors
Rodrigo A Fuentealba
Maria Ines Barría
Jiyeon Lee
Judy Cam
Claudia Araya
Claudia A Escudero
Nibaldo C Inestrosa
Francisca C Bronfman
Guojun Bu
Maria-Paz Marzolo
Publication date
01-12-2007
Publisher
BioMed Central
Published in
Molecular Neurodegeneration / Issue 1/2007
Electronic ISSN: 1750-1326
DOI
https://doi.org/10.1186/1750-1326-2-14

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