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International Journal of Alzheimer’s Disease
Volume 2011, Article ID 729382, 11 pages
http://dx.doi.org/10.4061/2011/729382
Research Article

TrkB Isoforms Differentially Affect AICD Production through Their Intracellular Functional Domains

Department of Biology, Drexel University, Philadelphia, PA 19027, USA

Received 2 September 2010; Revised 12 November 2010; Accepted 16 November 2010

Academic Editor: E. A. Rogaeva

Copyright © 2011 Sara Ansaloni et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

We report that NTRK2, the gene encoding for the TrkB receptor, can regulate APP metabolism, specifically AICD levels. Using the human neuroblastoma cell line SH-SY5Y, we characterized the effect of three TrkB isoforms (FL, SHC, T) on APP metabolism by knockdown and overexpression. We found that TrkB FL increases AICD-mediated transcription and APP levels while it decreases sAPP levels. These effects were mainly mediated by the tyrosine kinase activity of the receptor and partially by the PLC- 𝛾 - and SHC-binding sites. The TrkB T truncated isoform did not have significant effects on APP metabolism when transfected by itself, while the TrkB SHC decreased AICD-mediated transcription. TrkB T abolished TrkB FL effects on APP metabolism when cotransfected with it while TrkB SHC cotransfected with TrkB FL still showed increased APP levels. In conclusion, we demonstrated that TrkB isoforms have differential effects on APP metabolism.