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• Identification of distinct gamma-secretase complexes with different APH-1 variants.
• Citation:
  Shirotani K, Edbauer D, Prokop S, Haass C, Steiner H
  

  Identification of distinct gamma-secretase complexes with different APH-1 variants.

  The Journal of biological chemistry. 2004 Oct 1;279(40):41340-5
  [PubMed] [Alzforum]
• Supporting:
  • γ-secretase is biologically and biochemically heterogeneous, consisting of at least 4 or more different complexes.

    SHOW Details   Supporting(3)   Consistent(1) 

    Experimental Approach: Mechanism - biochemistry and structural biology,  
    Pathogenic Narrative Tags: Initial condition
    Supporting Evidence
    

    • Shirotani K, Edbauer D, Prokop S, Haass C, Steiner H
      Identification of distinct gamma-secretase complexes with different APH-1 variants.
      The Journal of biological chemistry. 2004 Oct 1;279(40):41340-5
    • Serneels L, Dejaegere T, Craessaerts K, Horré K, Jorissen E, Tousseyn T, Hébert S, Coolen M, Martens G, Zwijsen A, Annaert W, Hartmann D, De Strooper B
      Differential contribution of the three Aph1 genes to gamma-secretase activity in vivo.
      Proceedings of the National Academy of Sciences of the United States of America. 2005 Feb 1;102(5):1719-24
    • Hébert S, Serneels L, Dejaegere T, Horré K, Dabrowski M, Baert V, Annaert W, Hartmann D, De Strooper B
      Coordinated and widespread expression of gamma-secretase in vivo: evidence for size and molecular heterogeneity.
      Neurobiology of disease. 2004 Nov;17(2):260-72

    Consistent statements
    

    • Different γ-secretase complexes containing different Presenilin or Aph1 protein subunits are present in various tissues. Serneels L  Van Biervliet J  Craessaerts K  Dejaegere T  Horré K  Van Houtvin T  Esselmann H  Paul S  Schäfer M  Berezovska O  Hyman B  Sprangers B  Sciot R  Moons L  Jucker M  Yang Z  May P  Karran E  Wiltfang J  D'Hooge R  De Strooper B 
  • It is probable that different gamma-secretase complexes exert different biological and biochemical activities.

    SHOW Details   Supporting(3) 

    Experimental Approach: Mechanism - biochemistry and structural biology
    Pathogenic Narrative Tags: Initial condition
    Supporting Evidence
    

    • Hébert S, Serneels L, Dejaegere T, Horré K, Dabrowski M, Baert V, Annaert W, Hartmann D, De Strooper B
      Coordinated and widespread expression of gamma-secretase in vivo: evidence for size and molecular heterogeneity.
      Neurobiology of disease. 2004 Nov;17(2):260-72
    • De Strooper B
      Aph-1, Pen-2, and Nicastrin with Presenilin generate an active gamma-Secretase complex.
      Neuron. 2003 Apr 10;38(1):9-12
    • Shirotani K, Edbauer D, Prokop S, Haass C, Steiner H
      Identification of distinct gamma-secretase complexes with different APH-1 variants.
      The Journal of biological chemistry. 2004 Oct 1;279(40):41340-5
  • Two presenilin (PS1 and PS2) genes and two APH1 (APH1A and APH1B) genes, which are alternatively spliced, contribute to the heterogeneity of the complexes.

    SHOW Details   Supporting(2)   Consistent(1)     Genes/Proteins: (4)

    Experimental Approach: Mechanism - molecular and cell
    Pathogenic Narrative Tags: Initial condition
    Supporting Evidence
    

    • Shirotani K, Edbauer D, Prokop S, Haass C, Steiner H
      Identification of distinct gamma-secretase complexes with different APH-1 variants.
      The Journal of biological chemistry. 2004 Oct 1;279(40):41340-5
    • Hébert S, Serneels L, Dejaegere T, Horré K, Dabrowski M, Baert V, Annaert W, Hartmann D, De Strooper B
      Coordinated and widespread expression of gamma-secretase in vivo: evidence for size and molecular heterogeneity.
      Neurobiology of disease. 2004 Nov;17(2):260-72

    Consistent statements
    

    • It is likely that every γ-secretase complex contains 2 or more PS subunits. Bentahir M  Nyabi O  Verhamme J  Tolia A  Horré K  Wiltfang J  Esselmann H  De Strooper B 

    Genes/Proteins
    

    • Gene: PSEN1 presenilin 1 [Homo sapiens]
    • Gene: APH1B anterior pharynx defective 1 homolog B (C. elegans) [Homo sapiens]
    • Gene: PSEN2 presenilin 2 (Alzheimer disease 4) [Homo sapiens]
    • Gene: APH1A anterior pharynx defective 1 homolog A (C. elegans) [Homo sapiens]
  • Different γ-secretase complexes containing different Presenilin or Aph1 protein subunits are present in various tissues.

    SHOW Details   Supporting(2)   Consistent(1)     Genes/Proteins: (4)

    Experimental Approach: Mechanism - biochemistry and structural biology,   Mechanism - physiological systems
    Pathogenic Narrative Tags: Initial condition
    Supporting Evidence
    

    • Shirotani K, Edbauer D, Prokop S, Haass C, Steiner H
      Identification of distinct gamma-secretase complexes with different APH-1 variants.
      The Journal of biological chemistry. 2004 Oct 1;279(40):41340-5
    • Hébert S, Serneels L, Dejaegere T, Horré K, Dabrowski M, Baert V, Annaert W, Hartmann D, De Strooper B
      Coordinated and widespread expression of gamma-secretase in vivo: evidence for size and molecular heterogeneity.
      Neurobiology of disease. 2004 Nov;17(2):260-72

    Consistent statements
    

    • γ-secretase is biologically and biochemically heterogeneous, consisting of at least 4 or more different complexes. Bentahir M  Nyabi O  Verhamme J  Tolia A  Horré K  Wiltfang J  Esselmann H  De Strooper B 

    Genes/Proteins
    

    • Protein: Gamma-secretase subunit APH-1B [Homo sapiens]
    • Protein: Presenilin-2 [Homo sapiens]
    • Protein: Gamma-secretase subunit APH-1A [Homo sapiens]
    • Protein: Presenilin-1 [Homo sapiens]
• Created On: Wed, Apr 23 05:59:18 EDT 2008
• Last Modified On: Wed Apr 23 05:59:18 EDT 2008