The amyloid precursor protein intracellular domain(AICD) disrupts actin dynamics and mitochondrial bioenergetics.
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The amyloid precursor protein intracellular domain(AICD) disrupts actin dynamics and mitochondrial bioenergetics.

J Neurochem. 2010 Apr 1;113(1):275-84

Authors: Ward MW, Concannon CG, Whyte J, Walsh CM, Corley B, Prehn JH

The amyloid precursor protein (APP) is critically involved in the pathogenesis of Alzheimer's disease, and is strongly up-regulated in response to traumatic, metabolic, or toxic insults to the nervous system. The processing of APP by gamma/epsilon-secretase activity results in the generation of the APP intracellular domain (AICD). Previously, we have shown that AICD induces the expression of genes (transgelin, alpha2-actin) with functional roles in actin organization and dynamics and demonstrated that the induction of AICD and its co-activator Fe65 (AICD/Fe65) resulted in a loss of organized filamentous actin structures within the cell. As mitochondrial function is thought to be reliant on ordered actin dynamics, we examined mitochondrial function in human SHEP neuroblastoma cells inducibly expressing AICD/Fe65. Confocal analysis of the mitochondrial membrane potential (DeltaPsim) identified a significant decrease in the DeltaPsim in the AICD50/Fe65 over-expressing cells. This was paralleled by significantly reduced ATP levels and decreased basal superoxide production. Overexpression of the proposed AICD target gene transgelin in SHEP-SF parental cells and primary neurons was sufficient to destabilize actin filaments, depolarize DeltaPsim, and significantly alter mitochondrial distribution and morphology. Our data demonstrate that the induction of AICD/Fe65 or transgelin significantly alters actin dynamics and mitochondrial function in neuronal cells.

PMID: 20405578 [PubMed - in process]

Read the complete post at http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&db=PubMed&cmd=Retrieve&list_uids=20405578&dopt=Abstract

Posted 21 Apr 2010 3:54 AM by pubmed: neuroblastoma
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