Neurobiology of aging, 2012-04, Vol.33 (4), p.826.e15-826.e30
2012
Details
- Autor(en) / Beteiligte
- Titel
- Phosphorylation in the amino terminus of tau prevents inhibition of anterograde axonal transport
- Ist Teil von
- Neurobiology of aging, 2012-04, Vol.33 (4), p.826.e15-826.e30
- Ort / Verlag
- United States: Elsevier Inc
- Erscheinungsjahr
- 2012
- Link zum Volltext
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Abstract Alzheimer's disease (AD) and other tauopathies are characterized by fibrillar inclusions composed of the microtubule-associated protein, tau. Recently, we demonstrated that the N-terminus of tau (amino acids [aa] 2–18) in filamentous aggregates or N-terminal tau isoforms activate a signaling cascade involving protein phosphatase 1 and glycogen synthase kinase 3 that results in inhibition of anterograde fast axonal transport (FAT). We have termed the functional motif comprised of aa 2–18 in tau the phosphatase-activating domain (PAD). Here, we show that phosphorylation of tau at tyrosine 18, which is a fyn phosphorylation site within PAD, prevents inhibition of anterograde FAT induced by both filamentous tau and 6D tau. Moreover, Fyn-mediated phosphorylation of tyrosine 18 is reduced in disease-associated forms of tau (e.g., tau filaments). A novel PAD-specific monoclonal antibody revealed that exposure of PAD in tau occurs before and more frequently than tyrosine 18 phosphorylation in the evolution of tangle formation in AD. These results indicate that N-terminal phosphorylation may constitute a regulatory mechanism that controls tau-mediated inhibition of anterograde FAT in AD.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0197-4580eISSN: 1558-1497DOI: 10.1016/j.neurobiolaging.2011.06.006Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3272324
- Format
- –
- Schlagworte
- Alzheimer Disease - metabolism, Alzheimer Disease - pathology, Alzheimer's disease, Analysis of Variance, Animals, Axonal transport, Axonal Transport - drug effects, Axonal Transport - physiology, Brain - metabolism, Brain - pathology, Decapodiformes, Enzyme-Linked Immunosorbent Assay, Fyn kinase, Glycogen synthase kinase, Humans, Internal Medicine, Kinesin, Mutation - genetics, Neural Inhibition - drug effects, Neural Inhibition - physiology, Neurology, Phosphorylation, Protein Interaction Domains and Motifs - genetics, Protein Interaction Domains and Motifs - physiology, Protein Isoforms - chemistry, Protein Isoforms - metabolism, Protein phosphatase, Proto-Oncogene Proteins c-fyn - genetics, Proto-Oncogene Proteins c-fyn - metabolism, Signal Transduction, Tau filaments, tau Proteins - chemistry, tau Proteins - genetics, tau Proteins - metabolism, tau Proteins - pharmacology, Tauopathy, Time Factors, Tyrosine - metabolism, Tyrosine phosphorylation