Activation of GSK-3 and phosphorylation of CRMP2 in transgenic mice expressing APP intracellular domain

Amyloid precursor protein (APP), implicated in Alzheimer's disease, is a trans-membrane protein of undetermined function. APP is cleaved by γ-secretase that releases the APP intracellular domain (AICD) in the cytoplasm. In vitro studies have implicated AICD in cell signaling and transcriptional regulation, but its biologic relevance has been uncertain and its in vivo function has not been examined. To investigate its functional role, we generated AICD transgenic mice, and found that AICD causes significant biologic changes in vivo. AICD transgenic mice show activation of glycogen synthase kinase-3β (GSK-3β) and phosphorylation of CRMP2 protein, a GSK-3β substrate that plays a crucial role in Semaphorin3a-mediated axonal guidance. Our data suggest that AICD is biologically relevant, causes significant alterations in cell signaling, and may play a role in axonal elongation or pathfinding.

• Publication year

  2005

• Venue

  Journal of Cell Biology

• Publication date

  2005-10-24

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1083/jcb.200505078PMID 16230462PMCID 2171208
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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