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Involvement of 14‐3‐3 in tubulin instability and impaired axon development is mediated by Tau
Author(s) -
Joo Yuyoung,
Schumacher Benjamin,
Landrieu Isabelle,
Bartel Maria,
SmetNocca Caroline,
Jang Ahram,
Choi Hee Soon,
Jeon Noo Li,
Chang KeunA,
Kim HyeSun,
Ottmann Christian,
Suh YooHun
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.14-265009
Subject(s) - tauopathy , tau protein , microtubule , gene isoform , microbiology and biotechnology , microtubule associated protein , tubulin , neuroscience , phosphorylation , biology , chemistry , alzheimer's disease , neurodegeneration , biochemistry , disease , medicine , gene , pathology
14‐3‐3 proteins act as adapters that exert their function by interacting with their various protein partners. 14‐3‐3 proteins have been implicated in a variety of human diseases including neurodegenerative diseases. 14‐3‐3 proteins have recently been reported to be abundant in the neurofibrillary tangles (NFTs) observed inside the neurons of brains affected by Alzheimer's disease (AD). These NFTs are mainly constituted of phosphorylated Tau protein, a microtubule‐associated protein known to bind 14‐3‐3. Despite this indication of 14‐3‐3 protein involvement in the AD pathogenesis, the role of 14‐3‐3 in the Tauopathy remains to be clarified. In the present study, we shed light on the role of 14‐3‐3 proteins in the molecular pathways leading to Tauopathies. Overexpression of the 14‐3‐3ct isoform resulted in a disruption of the tubulin cytoskeleton and prevented neuritic outgrowth in neurons. NMR studies validated the phosphorylated residues pSer214 and pSer324 in Tau as the 2 primary sites for 14‐3‐3 binding, with the crystal structure of 14‐3‐3σ in complex with Tau‐pSer214 and Tau‐pSer324 revealing the molecular details of the interaction. These data suggest a rationale for a possible pharmacologic intervention of the Tau/14‐3‐3 interaction.—Joo, Y., Schumacher, B., Landrieu, I., Bartel, M., Smet‐Nocca, C., Jang, A., Choi, H. S., Jeon, N. L., Chang, K.‐A, Kim, H.‐S., Ottmann, C., Suh, Y.‐H. Involvement of 14‐3‐3 in tubulin instability and impaired axon development is mediated by Tau. FASEB J. 29, 4133‐4144 (2015). www.fasebj.org