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Apoptotic cell death and amyloid precursor protein signaling in neuroblastoma SH-SY5Y cells

Valentina Venezia1, Claudio Russo, Emanuela Repetto

  • 1Sezione di Farmacologia, Dipartimento Oncologia Biologia e Genetica, Università degli Studi di Genova, Italy.

Annals of the New York Academy of Sciences
|January 22, 2005
PubMed

Insights

Tyrosine-phosphorylated amyloid precursor protein (APP) and its fragments interact with ShcA-Grb2 adaptors. This interaction is disrupted during apoptosis, potentially contributing to Alzheimer

Area of Science:

  • Molecular and Cellular Biology
  • Neuroscience
  • Biochemistry

Background:

  • Amyloid precursor protein (APP) and its C-terminal fragments (CTFs) are tyrosine phosphorylated in human brain.
  • Tyrosine phosphorylation of APP/CTFs creates binding sites for ShcA and Grb2 adaptor proteins.
  • This interaction is notably enhanced in Alzheimer's disease (AD) brains.

Purpose of the Study:

  • To investigate APP/CTFs phosphorylation and ShcA activation in SH-SY5Y neuroblastoma cells.
  • To examine these molecular events under basal and apoptotic conditions induced by staurosporine.
  • To elucidate the role of APP processing and adaptor protein complex formation in apoptosis.

Main Methods:

  • Utilized staurosporine to induce apoptosis in SH-SY5Y cells.
  • Employed co-immunoprecipitation assays to detect protein-protein interactions.
  • Investigated the effects of caspase inhibitors on APP degradation and complex formation.

Main Results:

  • In proliferating cells, full-length APP complexes with Grb2 via its SH2 domain.
  • Apoptosis induction leads to APP degradation and co-immunoprecipitation of ShcA-Grb2 with CTFs.
  • Caspase inhibitors partially prevent APP degradation and CTF-adaptor complex formation.

Conclusions:

  • Tyrosine-phosphorylated APP forms a complex with ShcA-Grb2 adaptors, which is disrupted during apoptosis.
  • Abnormal APP degradation and increased CTFs in apoptosis generate complexes with intracellular adaptors.
  • APP and CTF signaling pathways are relevant to apoptotic cell death in Alzheimer's disease.

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