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Publication : The role of brain-derived neurotrophic factor (BDNF)-induced XBP1 splicing during brain development.

First Author  Hayashi A Year  2007
Journal  J Biol Chem Volume  282
Issue  47 Pages  34525-34
PubMed ID  17890727 Mgi Jnum  J:145222
Mgi Id  MGI:3834009 Doi  10.1074/jbc.M704300200
Citation  Hayashi A, et al. (2007) The role of brain-derived neurotrophic factor (BDNF)-induced XBP1 splicing during brain development. J Biol Chem 282(47):34525-34
abstractText  Accumulation of unfolded proteins in the endoplasmic reticulum initiates intracellular signaling termed the unfolded protein response (UPR). Although Xbp1 serves as a pivotal transcription factor for the UPR, the physiological role of UPR signaling and Xbp1 in the central nervous system remains to be elucidated. Here, we show that Xbp1 mRNA was highly expressed during neurodevelopment and activated Xbp1 protein was distributed throughout developing neurons, including neurites. The isolated neurite culture system and time-lapse imaging demonstrated that Xbp1 was activated in neurites in response to brain-derived neurotrophic factor (BDNF), followed by subsequent translocation of the active Xbp1 into the nucleus. BDNF-dependent neurite outgrowth was significantly attenuated in Xbp1(-/-) neurons. These findings suggest that BDNF initiates UPR signaling in neurites and that Xbp1, which is activated as part of the UPR, conveys the local information from neurites to the nucleus, contributing the neurite outgrowth.
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