Phosphorylation of the overlooked tyrosine 310 regulates the structure, aggregation, and microtubule- and lipid-binding properties of Tau.
Tau protein (Tau)
aggregation
amyloid
lipid binding
microtubule
neurodegenerative disease
phosphorylation
phosphotyrosine
post-translational modification (PTM)
tauopathy
Journal
The Journal of biological chemistry
ISSN: 1083-351X
Titre abrégé: J Biol Chem
Pays: United States
ID NLM: 2985121R
Informations de publication
Date de publication:
05 06 2020
05 06 2020
Historique:
received:
31
12
2019
revised:
22
04
2020
pubmed:
29
4
2020
medline:
29
12
2020
entrez:
29
4
2020
Statut:
ppublish
Résumé
The microtubule-associated protein Tau is implicated in the pathogenesis of several neurodegenerative disorders, including Alzheimer's disease. Increasing evidence suggests that post-translational modifications play critical roles in regulating Tau's normal functions and its pathogenic properties in tauopathies. Very little is known about how phosphorylation of tyrosine residues influences the structure, aggregation, and microtubule- and lipid-binding properties of Tau. Here, we sought to determine the relative contributions of phosphorylation of one or several of the five tyrosine residues in Tau (Tyr-18, -29, -197, -310, and -394) to the regulation of its biophysical, aggregation, and functional properties. We used a combination of site-specific mutagenesis and
Identifiants
pubmed: 32341125
pii: S0021-9258(17)49432-4
doi: 10.1074/jbc.RA119.012517
pmc: PMC7278352
doi:
Substances chimiques
Lipids
0
MAPT protein, human
0
tau Proteins
0
Tyrosine
42HK56048U
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
7905-7922Subventions
Organisme : NIA NIH HHS
ID : R37 AG019391
Pays : United States
Organisme : NIH HHS
ID : S10 OD016320
Pays : United States
Informations de copyright
© 2020 Ait-Bouziad et al.
Déclaration de conflit d'intérêts
Conflict of interest—Prof. Hilal Lashuel is the founder and chief scientific officer of ND BioSciences SA.
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