Open AccessTrkB Isoforms Differentially Affect AICD Production through Their Intracellular Functional Domains
Author(s) -
Sara Ansaloni,
Brian Leung,
Neeraj P. Sebastian,
Rohini Samudralwar,
Mariana C. Gadaleta,
Aleister J. Saunders
Publication year - 2011
Publication title -
international journal of alzheimer s disease
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.657
H-Index - 49
eISSN - 2090-8024
pISSN - 2090-0252
DOI - 10.4061/2011/729382
Subject(s) - tropomyosin receptor kinase b , gene isoform , gene knockdown , receptor , microbiology and biotechnology , transfection , tyrosine kinase , chemistry , tropomyosin receptor kinase a , receptor tyrosine kinase , biology , neurotrophin , signal transduction , neurotrophic factors , gene , biochemistry
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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