Interaction of ASK1 and the β-amyloid precursor protein in a stress-signaling complex

Veronica Galvan, Surita Banwait, Patricia Spilman, Olivia F. Gorostiza, Alyson Peel, Marina Ataie, Danielle Crippen, Wei Huang, Gurleen Sidhu, Hidenori Ichijo, Dale E. Bredesen

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

The amyloid precursor protein (APP) is a type I transmembrane protein translocated to neuronal terminals, whose function is still unknown. The C-terminus of APP mediates its interaction with cellular adaptor and signaling proteins, some of which signal to the stress-activated protein kinase (SAPK) pathway. Here we show that ASK1, a MAPKKK that activates two SAPKs, c-Jun N-terminal-kinase (JNK) and p38, is present in a complex containing APP, phospho-MKK6, JIP1 and JNK1. In primary neurons deprived of growth factors, as well as in brains of (FAD)APP-transgenic mice, ASK1 was upregulated in neuronal projections, where it interacted with APP. In non-transgenic brains, ASK1 and APP associated mainly in the ER. Our results indicate that recruitment of ASK1 to stress-signaling complexes assembled with APP may be triggered and enhanced by cellular stress. Thus, ASK1 may be the apical MAPKKK in a signaling complex assembled with APP as a response to stress.

Original languageEnglish (US)
Pages (from-to)65-75
Number of pages11
JournalNeurobiology of Disease
Volume28
Issue number1
DOIs
StatePublished - Oct 1 2007
Externally publishedYes

Keywords

  • Alzheimer's disease
  • Amyloid precursor protein
  • Apoptosis signaling kinase
  • Neurodegeneration
  • Stress signaling complex

ASJC Scopus subject areas

  • Neurology

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  • Cite this

    Galvan, V., Banwait, S., Spilman, P., Gorostiza, O. F., Peel, A., Ataie, M., Crippen, D., Huang, W., Sidhu, G., Ichijo, H., & Bredesen, D. E. (2007). Interaction of ASK1 and the β-amyloid precursor protein in a stress-signaling complex. Neurobiology of Disease, 28(1), 65-75. https://doi.org/10.1016/j.nbd.2007.06.017