Home LiteratureArticle Details
PMID: 18650430 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Review

Amyloid precursor protein trafficking, processing, and function.

The Journal of biological chemistry ·Vol. 283 ·No. 44 ·2008-10-31 ·Pages 29615-9

Thinakaran G, Koo EH

Abstract

Intracellular trafficking and proteolytic processing of amyloid precursor protein (APP) have been the focus of numerous investigations over the past two decades. APP is the precursor to the amyloid beta-protein (Abeta), the 38-43-amino acid residue peptide that is at the heart of the amyloid cascade hypothesis of Alzheimer disease (AD). Tremendous progress has been made since the initial identification of Abeta as the principal component of brain senile plaques of individuals with AD. Specifically, molecular characterization of the secretases involved in Abeta production has facilitated cell biological investigations on APP processing and advanced efforts to model AD pathogenesis in animal models. This minireview summarizes salient features of APP trafficking and amyloidogenic processing and discusses the putative biological functions of APP.

MeSH Terms
Alzheimer Disease/metabolism Amino Acid Sequence Amino Acids/chemistry Amyloid/chemistry Amyloid Precursor Protein Secretases/metabolism Animals Biological Transport Brain/metabolism Cell Adhesion Endocytosis Humans Models, Biological Molecular Sequence Data Protein Structure, Tertiary Protein Transport
Chemicals
Amino Acids Amyloid Amyloid Precursor Protein Secretases
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Thinakaran Gopal
Department of Neurobiology, The University of Chicago, Chicago, Illinois 60637, USA. [email protected]
Koo Edward H
References (54)
54 references, click to expand
  1. Presenilin: running with scissors in the membrane.
    Cell. 2007 Oct 19;131(2):215-21 PMID: 17956719
  2. Compartmentalization of beta-secretase (Asp2) into low-buoyant density, noncaveolar lipid rafts.
    Curr Biol. 2001 Aug 21;11(16):1288-93 PMID: 11525745
  3. Spatial segregation of gamma-secretase and substrates in distinct membrane domains.
    J Biol Chem. 2005 Jul 8;280(27):25892-900 PMID: 15886206
  4. Soluble form of amyloid precursor protein regulates proliferation of progenitors in the adult subventricular zone.
    Development. 2004 May;131(9):2173-81 PMID: 15073156
  5. Alzheimer amyloid protein precursor in the rat hippocampus: transport and processing through the perforant path.
    J Neurosci. 1998 Dec 1;18(23):9629-37 PMID: 9822724
  6. The gamma-secretase complex: machinery for intramembrane proteolysis.
    Curr Opin Neurobiol. 2004 Jun;14(3):379-83 PMID: 15194119
  7. FE65 constitutes the functional link between the low-density lipoprotein receptor-related protein and the amyloid precursor protein.
    J Neurosci. 2004 Apr 28;24(17):4259-65 PMID: 15115822
  8. Dissection of amyloid-beta precursor protein-dependent transcriptional transactivation.
    J Biol Chem. 2004 Jun 4;279(23):24601-11 PMID: 15044485
  9. A 109-amino-acid C-terminal fragment of Alzheimer's-disease amyloid precursor protein contains a sequence, -RHDS-, that promotes cell adhesion.
    Biochem J. 1992 Dec 15;288 ( Pt 3):1053-9 PMID: 1281980
  10. Phosphorylation-dependent regulation of the interaction of amyloid precursor protein with Fe65 affects the production of beta-amyloid.
    J Biol Chem. 2001 Oct 26;276(43):40353-61 PMID: 11517218
  11. The X11 proteins, Abeta production and Alzheimer's disease.
    Trends Neurosci. 2006 May;29(5):280-5 PMID: 16545469
  12. Binding of F-spondin to amyloid-beta precursor protein: a candidate amyloid-beta precursor protein ligand that modulates amyloid-beta precursor protein cleavage.
    Proc Natl Acad Sci U S A. 2004 Feb 24;101(8):2548-53 PMID: 14983046
  13. Gamma-secretase: proteasome of the membrane?
    Nat Rev Mol Cell Biol. 2004 Jun;5(6):499-504 PMID: 15173829
  14. Evidence that production and release of amyloid beta-protein involves the endocytic pathway.
    J Biol Chem. 1994 Jul 1;269(26):17386-9 PMID: 8021238
  15. Amyloid precursor protein regulates brain apolipoprotein E and cholesterol metabolism through lipoprotein receptor LRP1.
    Neuron. 2007 Oct 4;56(1):66-78 PMID: 17920016
  16. Reduced synaptic vesicle density and active zone size in mice lacking amyloid precursor protein (APP) and APP-like protein 2.
    Neurosci Lett. 2005 Aug 12-19;384(1-2):66-71 PMID: 15919150
  17. Amyolid precursor protein mediates presynaptic localization and activity of the high-affinity choline transporter.
    Proc Natl Acad Sci U S A. 2007 Aug 28;104(35):14140-5 PMID: 17709753
  18. A TAG1-APP signalling pathway through Fe65 negatively modulates neurogenesis.
    Nat Cell Biol. 2008 Mar;10(3):283-94 PMID: 18278038
  19. A transcriptionally [correction of transcriptively] active complex of APP with Fe65 and histone acetyltransferase Tip60.
    Science. 2001 Jul 6;293(5527):115-20 PMID: 11441186
  20. beta-Amyloid precursor protein-deficient mice show reactive gliosis and decreased locomotor activity.
    Cell. 1995 May 19;81(4):525-31 PMID: 7758106
  21. ADAMs family members as amyloid precursor protein alpha-secretases.
    J Neurosci Res. 2003 Nov 1;74(3):342-52 PMID: 14598310
  22. Munc18 interacting proteins: ADP-ribosylation factor-dependent coat proteins that regulate the traffic of beta-Alzheimer's precursor protein.
    J Biol Chem. 2003 Sep 19;278(38):36032-40 PMID: 12842896
  23. SorLA/LR11 regulates processing of amyloid precursor protein via interaction with adaptors GGA and PACS-1.
    J Biol Chem. 2007 Nov 9;282(45):32956-64 PMID: 17855360
  24. Exchange of N-CoR corepressor and Tip60 coactivator complexes links gene expression by NF-kappaB and beta-amyloid precursor protein.
    Cell. 2002 Jul 12;110(1):55-67 PMID: 12150997
  25. Defective neuromuscular synapses in mice lacking amyloid precursor protein (APP) and APP-Like protein 2.
    J Neurosci. 2005 Feb 2;25(5):1219-25 PMID: 15689559
  26. The functions of mammalian amyloid precursor protein and related amyloid precursor-like proteins.
    Neurodegener Dis. 2006;3(4-5):239-46 PMID: 17047363
  27. APP processing is regulated by cytoplasmic phosphorylation.
    J Cell Biol. 2003 Oct 13;163(1):83-95 PMID: 14557249
  28. Amyloid precursor protein regulates differentiation of human neural stem cells.
    Stem Cells Dev. 2006 Jun;15(3):381-9 PMID: 16846375
  29. BACE1: the beta-secretase enzyme in Alzheimer's disease.
    J Mol Neurosci. 2004;23(1-2):105-14 PMID: 15126696
  30. Association of gamma-secretase with lipid rafts in post-Golgi and endosome membranes.
    J Biol Chem. 2004 Oct 22;279(43):44945-54 PMID: 15322084
  31. Fasciclin II signals new synapse formation through amyloid precursor protein and the scaffolding protein dX11/Mint.
    J Neurosci. 2005 Jun 22;25(25):5943-55 PMID: 15976083
  32. Age-related cognitive deficits, impaired long-term potentiation and reduction in synaptic marker density in mice lacking the beta-amyloid precursor protein.
    Neuroscience. 1999 Apr;90(1):1-13 PMID: 10188929
  33. Memory-enhancing effects of secreted forms of the beta-amyloid precursor protein in normal and amnestic mice.
    Proc Natl Acad Sci U S A. 1998 Oct 13;95(21):12683-8 PMID: 9770546
  34. Presenilin-dependent transcriptional control of the Abeta-degrading enzyme neprilysin by intracellular domains of betaAPP and APLP.
    Neuron. 2005 May 19;46(4):541-54 PMID: 15944124
  35. APL-1, a Caenorhabditis elegans protein related to the human beta-amyloid precursor protein, is essential for viability.
    Proc Natl Acad Sci U S A. 2007 Feb 6;104(6):1971-6 PMID: 17267616
  36. Cortical dysplasia resembling human type 2 lissencephaly in mice lacking all three APP family members.
    EMBO J. 2004 Oct 13;23(20):4106-15 PMID: 15385965
  37. Secreted form of amyloid beta protein precursor is involved in the growth regulation of fibroblasts.
    Cell. 1989 Aug 25;58(4):615-22 PMID: 2475254
  38. Increased expression of beta-amyloid precursor protein during neuronal differentiation is not accompanied by secretory cleavage.
    Proc Natl Acad Sci U S A. 1992 Oct 15;89(20):9439-43 PMID: 1409654
  39. Sorting through the cell biology of Alzheimer's disease: intracellular pathways to pathogenesis.
    Neuron. 2006 Oct 5;52(1):15-31 PMID: 17015224
  40. Axonal transport, amyloid precursor protein, kinesin-1, and the processing apparatus: revisited.
    J Neurosci. 2005 Mar 2;25(9):2386-95 PMID: 15745965
  41. Amino acid sequence RERMS represents the active domain of amyloid beta/A4 protein precursor that promotes fibroblast growth.
    J Cell Biol. 1993 May;121(4):879-86 PMID: 8491779
  42. Presenilin/gamma-secretase-dependent processing of beta-amyloid precursor protein regulates EGF receptor expression.
    Proc Natl Acad Sci U S A. 2007 Jun 19;104(25):10613-8 PMID: 17556541
  43. Amyloidogenic processing of the Alzheimer beta-amyloid precursor protein depends on lipid rafts.
    J Cell Biol. 2003 Jan 6;160(1):113-23 PMID: 12515826
  44. Cellular actions of beta-amyloid precursor protein and its soluble and fibrillogenic derivatives.
    Physiol Rev. 1997 Oct;77(4):1081-132 PMID: 9354812
  45. The amyloid precursor protein of Alzheimer's disease is found on the surface of static but not activity motile portions of neurites.
    Brain Res. 1996 Sep 30;735(1):59-66 PMID: 8905170
  46. Beta-amyloid precursor protein cleavage by a membrane-bound protease.
    Proc Natl Acad Sci U S A. 1992 Jul 1;89(13):6075-9 PMID: 1631093
  47. Axonal transport of amyloid precursor protein is mediated by direct binding to the kinesin light chain subunit of kinesin-I.
    Neuron. 2000 Nov;28(2):449-59 PMID: 11144355
  48. The neuronal sortilin-related receptor SORL1 is genetically associated with Alzheimer disease.
    Nat Genet. 2007 Feb;39(2):168-77 PMID: 17220890
  49. A critical function for beta-amyloid precursor protein in neuronal migration revealed by in utero RNA interference.
    J Neurosci. 2007 Dec 26;27(52):14459-69 PMID: 18160654
  50. Crystal structure of the N-terminal, growth factor-like domain of Alzheimer amyloid precursor protein.
    Nat Struct Biol. 1999 Apr;6(4):327-31 PMID: 10201399
  51. Cell surface amyloid beta-protein precursor colocalizes with beta 1 integrins at substrate contact sites in neural cells.
    J Neurosci. 1997 Feb 1;17(3):1004-10 PMID: 8994055
  52. Increase of synaptic density and memory retention by a peptide representing the trophic domain of the amyloid beta/A4 protein precursor.
    Proc Natl Acad Sci U S A. 1994 Aug 2;91(16):7450-4 PMID: 8052602
  53. Precursor of amyloid protein in Alzheimer disease undergoes fast anterograde axonal transport.
    Proc Natl Acad Sci U S A. 1990 Feb;87(4):1561-5 PMID: 1689489
  54. Mutagenesis identifies new signals for beta-amyloid precursor protein endocytosis, turnover, and the generation of secreted fragments, including Abeta42.
    J Biol Chem. 1999 Jul 2;274(27):18851-6 PMID: 10383380
Article Info
Journal
The Journal of biological chemistry
Abbr.
J Biol Chem
ISSN
0021-9258
DOI
10.1074/jbc.R800019200
Email
[email protected]
Published
2008-10-31
Epub
2008-00-23
Pages
29615-9
Language
English
Region
United States
NLM ID
2985121R
PMCID
PMC2573065
Subset
IM
Grants
NIA NIH HHS · AG12376 · United States
NIA NIH HHS · AG021495 · United States
NIA NIH HHS · AG019070 · United States
NIA NIH HHS · R01 AG021495 · United States
NIA NIH HHS · R01 AG019070 · United States
NIA NIH HHS · AG032179 · United States
External Links
PubMed source DOI: 10.1074/jbc.R800019200 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2