Transmembrane APP is Distributed into Two Pools and Associated with Polymerized Cytoskeleton

  • B. Allinquant
  • K. L. Moya
  • C. Bouillot
  • A. Prochiantz
Conference paper
Part of the Research and Perspectives in Alzheimer’s Disease book series (ALZHEIMER)

Abstract

βA4 peptide is the major component of extracellular amyloid deposits present in the brain of patients with Alzheimer’s disease. The sequence of βA4 indicates that it is cleaved from the larger amyloid precursor protein (APP). APP is encoded by a single gene which yields, by alternative splicing, three major isoforms designated APP770, APP751, APP695. Sequence analysis suggests that APP is a transmembrane protein having a long N-terminal extracellular domain, a transmembrane region and a short cytoplasmic tail (Kang et al. 1987).

Keywords

Paraformaldehyde Glycosaminoglycan A23187 Eisen Mellon 

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References

  1. Breen KC, Bruce M, Anderton BH (1991) Beta amyloid precursor protein mediates neuronal cell-cell and cell-surface adhesion. J Neurosci Res 28: 90–100PubMedCrossRefGoogle Scholar
  2. Esch FS, Keim EC, Blacher RW, Culwell AR, Oltersdorf T, McClure D, Ward PJ (1990) Cleavage of amyloid β peptide during constitutive processing of its precursor. Science 248: 1122–1124PubMedCrossRefGoogle Scholar
  3. Estus S, Golde TE, Kunishita T, Blades D, Lowery D, Eisen M, Usiak M, Qu X, Tabira T, Greenberg BD, Younkin SG (1992) Potentially amyloidogenic, carboxyl-terminal derivatives of the amyloid protein precursor. Science 255: 726–728PubMedCrossRefGoogle Scholar
  4. Golde TE, Estus S, Younkin LH, Selkoe DJ, Younkin SG (1992) Processing of the amyloid protein precursor to potentially amyloidogenic derivatives. Science 255: 728–730PubMedCrossRefGoogle Scholar
  5. Haass C, Hung AY, Selkoe DJ (1991) Processing of β-amyloid precursor protein in microglia and astrocytes favors an internal localization over constitutive secretion. J Neurosci 11: 3783–3793PubMedGoogle Scholar
  6. Haass C, Schlossmacher MG, Hung AY, Vigo-Pelfrey C, Mellon A, Ostaszewski BL, Lieberburg I, Koo EH, Schenk D, Teplow DB, Selkoe DJ (1992) Amyloid β-peptide is produced by cultured cells during normal metabolism. Nature 359: 322–325PubMedCrossRefGoogle Scholar
  7. Hung AY, Koo EH, Haass C, Selkoe DJ (1992) Increased expression of β-amyloid precursor protein during neuronal differentiation is not accompanied by secretory cleavage. Proc Natl Acad Sci USA 89:9439–9443PubMedCrossRefGoogle Scholar
  8. Kang J, Lemaire HG, Unterbeck A, Salbaum JM, Masters CL, Grzeschik KH, Multhaup G, Beyreuther K, Müller-Hill B (1987) The precursor of Alzheimer’s disease amyloid A4 protein resembles a cell-surface receptor. Nature 325: 733–736PubMedCrossRefGoogle Scholar
  9. Klier FG, Cole G, Stallcup W, Schubert D (1992) Amyloid β-protein precursor is associated with extracellular matrix. Brain Res. 515: 336–342CrossRefGoogle Scholar
  10. Lafont F, Rouget M, Triller A, Prochiantz A, Rousselet A (1992) In vitro control of neuronal polarity by glycosaminoglycans. Development 114:17–29PubMedGoogle Scholar
  11. Martin LJ, Sisodia SS, Koo EH, Cork LC, Dellovade TL, Weidemann, A, Beyreuther K, Masters C, Price DL (1991) Amyloid precursor protein in aged nonhuman primates. Proc Natl Acad Sci USA 88: 1461–1465PubMedCrossRefGoogle Scholar
  12. Moya KL, Benowitz LI, Schneider GE, Allinquant B (1994) The amyloid precursor protein is developmentally regulated and correlated with synaptogenesis. Dev Biology 161: 597–603CrossRefGoogle Scholar
  13. Nordstedt C, Caporaso GL, Thyberg J, Gandy SE, Greengard P (1993) Identification of the Alzheimer β/A4 amyloid precursor protein in clathrin-coated vesicles purified from PC 12 cells. J Biol Chem 268: 608–612PubMedGoogle Scholar
  14. Palmert MR, Podlisny MB, Witker DS, Olderstorf T, Younkin LH, Selkoe DJ, Younkin SG (1989) The β-amyloid protein precursor of alzheimer disease has soluble derivatives found in human brain and cerebrospinal fluid. Proc Natl Acad Sci USA 86: 6338–6342PubMedCrossRefGoogle Scholar
  15. Refolo LM, Wittenberg IS, Friedrich Jr VL, Robakis NK (1991) The Alzheimer amyloid precursor is associated with the detergent-insoluble cytoskeleton. J Neurosci 11: 3888–3897PubMedGoogle Scholar
  16. Schubert D (1991) The possible role of adhesion in synaptic modification. Trends Neurosci 15: 127–130CrossRefGoogle Scholar
  17. Schubert D, Jin LW, Saitoh T, Cole G (1989) The regulation of amyloid β protein precursor secretion and its modulatory role in cell adhesion. Neuron 3: 689–694PubMedCrossRefGoogle Scholar
  18. Shubert W, Prior R, Weidemann A, Dircksen H, Multhaup G, Masters CL, Beyreuther K (1991) Localization of Alzheimer βA4 amyloid precursor protein at central and peripheral synaptic sites. Brain Res 563: 184–194CrossRefGoogle Scholar
  19. Seubert P, Vigo-Pelfrey C, Esch F, Lee M, Dovey H, Davis D, Sinha S, Schlossmacher M, Whaley J, Swindlehurst C, McCormack R, Wolfert R, Selkoe D, Lieberburg I, Schenk D (1992) Isolation and quantification of soluble Alzheimer’s β-peptide from biological fluids. Nature 359: 325–327PubMedCrossRefGoogle Scholar
  20. Seubert P, Oltersdorf T, Lee MG, Barbour R, Blomquist C, Davis DL, Bryant, K, Fritz LC, Galasko D, Thal LJ, Lieberburg I, Schenk DB (1993) Secretion of β-amyloid precursor protein cleaved at the amino terminus of the β-amyloid peptide Nature 361: 260–263PubMedCrossRefGoogle Scholar
  21. Sisodia SS (1992) β-Amyloid precursor protein cleavage by a membrane-bound protease. Proc Natl Acad Sci USA 89: 6075–6079PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1994

Authors and Affiliations

  • B. Allinquant
    • 1
  • K. L. Moya
  • C. Bouillot
  • A. Prochiantz
  1. 1.CNRS, URA 1414, ENSParisFrance

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