Activation of GSK-3 and Phosphorylation of CRMP2 in Transgenic Mice Expressing APP Intracellular Domain

Overview

Journal J Cell Biol

Specialty Cell Biology

Date 2005 Oct 19

PMID 16230462

Citations 79

Authors

Kathleen A Ryan

Sanjay W Pimplikar

Affiliations

Soon will be listed here.

Abstract

Amyloid precursor protein (APP), implicated in Alzheimer's disease, is a trans-membrane protein of undetermined function. APP is cleaved by gamma-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-3beta (GSK-3beta) and phosphorylation of CRMP2 protein, a GSK-3beta 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.

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