2010 •
TrkB Isoforms Differentially Affect AICD Production through Their Intracellular Functional Domains
Authors:
Sara Ansaloni, Brian P. Leung, Neeraj P. Sebastian, Rohini Samudralwar, Mariana C. Gadaleta, Aleister J. Saunders
Abstract:We report thatNTRK2, 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 s (...) We report thatNTRK2, 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.(Read More)
Sara Ansaloni, Brian P. Leung, Neeraj P. Sebastian, Rohini Samudralwar, Mariana Gadaleta, Aleister J (...)
International Journal of Alzheimer's Disease ·
2011
Cell biology |
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