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TrkB Isoforms Differentially Affect AICD Production through Their Intracellular Functional Domains
Journal article   Open access   Peer reviewed

TrkB Isoforms Differentially Affect AICD Production through Their Intracellular Functional Domains

Sara Ansaloni, Brian P. Leung, Neeraj P. Sebastian, Rohini Samudralwar, Mariana Gadaleta and Aleister J. Saunders
International journal of alzheimer's disease, v 2011, 729382
2011
PMID: 21423675
url
https://doi.org/10.4061/2011/729382View
Published, Version of Record (VoR) Open

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-- 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.

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