Modulation of gene expression and cytoskeletal dynamics by the amyloid precursor protein intracellular domain (AICD)

Thorsten Müller*, Caoimhin G. Concannon, Manus W. Ward, Ciara M. Walsh, Anca L. Tirniceriu, Florian Tribl, Donat Kögel, Jochen H.M. Prehn, Rupert Egensperger

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

122 Scopus citations


Amyloidogenic processing of the amyloid precursor protein (AFF) results in the generation of β-amyloid, the main constituent of Alzheimer plaques, and the APP intracellular domain (AICD). Recently, it has been demonstrated that AICD has transactivation potential; however, the targets of AICD-dependent gene regulation and hence the physiological role of AICD remain largely unknown. We analyzed transcriptome changes during AICD-dependent gene regulation by using a human neural cell culture system inducible for expression of AICD, its coactivator FE65, or the combination of both. Induction of AICD was associated with increased expression of genes with known function in the organization and dynamics of the actin cytoskeleton, including α2-Actin and Transgelin (SM22). AICD target genes were also found to be differentially regulated in the frontal cortex of Alzheimer's disease patients compared with controls as well as in AICD/FE65 transiently transfected murine cortical neurons. Confocal image analysis of neural cells and cortical neurons expressing both AICD and FE65 confirmed pronounced changes in the organization of the actin cytoskeleton, including the destabilization of actin fibers and clumping of actin at the sites of cellular outgrowth. Our data point to a role of AICD in developmental and injury-related cytoskeletal dynamics in the nervous system.

Original languageEnglish (US)
Pages (from-to)201-210
Number of pages10
JournalMolecular Biology of the Cell
Issue number1
StatePublished - Jan 2007
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology


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