Logo image
Back
TrkB isoforms differentially regulate amyloid precursor protein Swedish mutant glycosylation and processing
Abstract   Peer reviewed

TrkB isoforms differentially regulate amyloid precursor protein Swedish mutant glycosylation and processing

Sara Ansaloni, Brian Leung, Mariana Gadaleta and Aleister Saunders
Alzheimer's & dementia, v 7(4), pp S579-S579
Jul 2011
DOI: https://doi.org/10.1016/j.jalz.2011.05.1638

Abstract

Background NTRK2 encodes the neurotrophin receptor TrkB that binds Brain Derived Neurothrophic Factor (BDNF). TrkB/BDNF signaling is important for neuronal functions and long-term potentiation and is impaired by Abeta. Therefore TrkB/BDNF signaling may be biologically relevant to Alzheimer's Disease (AD). Alternative splicing of the NTRK2 mRNA results in at least three major receptor isoforms, TrkB FL, TrkB SHC and TrkB T. All of these bind BDNF and are co-expressed on the surface of neurons. While the TrkB FL isoform has been investigated for its role in AD, the two truncated isoforms and their interation with TrkB FL has not been extensively investigated, especially theTrkB SHC isoform. Methods We have previously shown that the TrkB isoforms can differentially affect AICD-mediated luciferase activity in a human neuroblastoma cell line. The goal of this study is to investigate the effects of the TrkB isoforms on the APP Swedish mutant in a TrkB and BDNF free human cell line. We employed site directed mutagenesis to identify the intracellular functional sites responsible for the observed effects. We also aimed at elucidating the effects of the interaction between the TrkB isoforms and the APP Swedish mutant. Results We found that TrkB FL over-expression increased APP FL levels, decreased APP glycosylation and decreased C99/C83 levels compared to the truncated isoforms. These effects were BDNF independent but dependent on the tyrosine kinase activity of the FL receptor. We also found that co-expression of the TrkB FL receptor with the truncated isoforms can modulate its effect on APP. In particular TrkB T completely eliminated the effects of TrkB FL whileTrkB SHC did not. Conclusions These results suggest that TrkB isoforms differentially regulate APP metabolism. Studies on primary neurons should follow these initial promising results since all of the investigated isoforms are co-expressed in neurons. The regulation of the truncated TrkBisoforms on TrkB FL is particularly interesting as TrkB FL/BDNF signaling has been shown to be beneficial for ameliorating cognitive deficits.

Metrics

16 Record Views

Details

Logo image