Modulation of Rack-1/PKCβII signalling by soluble AβPPα in SH-SY5Y cells

Erica Buoso, Fabrizio Biundo, Cristina Lanni, Stefania Aiello, Serena Grossi, Gennaro Schettini, Stefano Govoni, Marco Racchi

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

The soluble amyloid β precursor protein α (sAβPPα) released after α-secretase cleavage of the amyloid β precursor protein (AβPP) has several functions including modulation of neuronal excitability and synaptic plasticity; it has been suggested that some of these effects are mediated by activation of NF-κB via induction of PI3K/Akt signaling pathway. We have recently described the presence of several consensus binding sites of c-Rel transcription factor in the promoter region of the GNB2L1 gene, coding for the Receptor for Activated C Kinase -1 (RACK-1). We investigated whether sAβPPα could influence the expression of RACK-1 through NF-kappa;B involvement. Our data demonstrate that sAβPPα regulates RACK-1 gene expression through PI3K/Akt-dependent pathway, inducing c-Rel nuclear translocation and NF-κB activation. Since RACK-1 is the scaffold of protein kinase βpII (PKCβII), we turned our attention to this kinase in order to evaluate whether sAβPPα could also influence PKCpII signalling demonstrating that sAβPPα induces PKCβII translocation and interaction with its scaffold with consequent RACK-1/PKCβII complex increase in membrane. Altogether these results suggest the existence of an interesting loop between the functions of the metabolic products of AβPP and the role of PKC and that the impact of a dysregulated AβPP metabolism occurring in several conditions (from physiological aging to injury response) may have consequences on the potential protective functions of the non amyloidogenic sAβPPα.

Original languageEnglish (US)
Pages (from-to)697-705
Number of pages9
JournalCurrent Alzheimer research
Volume10
Issue number7
DOIs
StatePublished - Nov 29 2013
Externally publishedYes

Keywords

  • NF-κB
  • PI3K-AKt
  • Protein kinase C βII
  • RACK-1
  • Signal transduction
  • sAPPα

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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