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Brain‐derived neurotrophic factor induces a rapid dephosphorylation of tau protein through a PI‐3Kinase signalling mechanism
Author(s) -
Elliott Evan,
Atlas Roee,
Lange Aya,
Ginzburg Irith
Publication year - 2005
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/j.1460-9568.2005.04290.x
Subject(s) - dephosphorylation , phosphorylation , tropomyosin receptor kinase b , trk receptor , hyperphosphorylation , microbiology and biotechnology , neurotrophic factors , tau protein , brain derived neurotrophic factor , wortmannin , biology , kinase , chemistry , receptor , medicine , alzheimer's disease , biochemistry , phosphatase , protein kinase b , disease
Abstract The microtubule‐associated protein tau is essential for microtubule stabilization in neuronal axons. Hyperphosphorylation and intracellular fibrillar formation of tau protein is a pathology found in Alzheimer's disease (AD) brains, and in a variety of neurodegenerative disorders referred to as ‘taupathies’. In the present study, we investigated how brain‐derived neurotrophic factor (BDNF), an extracellular factor that is down‐regulated in AD brains, affects tau phosphorylation. BDNF stimulation of neuronally differentiated P19 mouse embryonic carcinoma cells resulted in a rapid decrease in tau phosphorylation, at phosphorylation sites recognized by Tau1, AT8, AT180 and p262‐Tau antibodies. K252a, a tyrosine receptor kinase (Trk) inhibitor, attenuated this dephosphorylation event, suggesting that BNDF activation of TrkB is responsible for the tau dephosphorylation. In addition, BDNF had no affect on tau phosphorylation in the presence of wortmannin, a PI‐3Kinase inhibitor, or lithium, a GSK3β inhibitor, suggesting that these two kinases are part of the signaling transduction cascade leading from TrkB receptor activation to tau dephosphorylation. These results suggest a link between a correlate of AD, decrease in BDNF levels and an AD pathology, tau hyperphosphorylation.