TrkB Isoforms Differentially Affect AICD Production through Their Intracellular Functional Domains

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...

Full description

Saved in:
Bibliographic Details
Published in:International journal of alzheimer's disease 2011, Vol.2011 (2011), p.1-11
Main Authors: Leung, Brian P., Ansaloni, Sara, Sebastian, Neeraj P., Samudralwar, Rohini, Gadaleta, Mariana, Saunders, Aleister J.
Format: Article
Language:English
Subjects:
Genes
Metabolism
Physiological aspects
Protein kinases
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:2090-8024
2090-0252
2090-0252
DOI:10.4061/2011/729382