Presence of a carboxy-terminal pseudorepeat and disease-like pseudohyperphosphorylation critically influence tau's interaction with microtubules in axon-like processes

Autor(en): Niewidok, Benedikt
Igaev, Maxim
Suendermann, Frederik
Janning, Dennis
Bakota, Lidia
Brandt, Roland 
Stichwörter: ALZHEIMERS-DISEASE; AMYLOID-BETA; Cell Biology; CELL-DEATH; FRONTOTEMPORAL-DEMENTIA; FULL-LENGTH TAU; HIDDEN MARKOV-MODELS; HIPPOCAMPAL-NEURONS; IN-VIVO; PAIRED HELICAL FILAMENTS; PROTEIN-TAU
Erscheinungsdatum: 2016
Herausgeber: AMER SOC CELL BIOLOGY
Journal: MOLECULAR BIOLOGY OF THE CELL
Volumen: 27
Ausgabe: 22
Startseite: 3537
Seitenende: 3549
Zusammenfassung: 
A current challenge of cell biology is to investigate molecular interactions in subcellular compartments of living cells to overcome the artificial character of in vitro studies. To dissect the interaction of the neuronal microtubule (MT)-associated protein tau with MTs in axon-like processes, we used a refined fluorescence decay after photoactivation approach and single-molecule tracking. We found that isoform variation had only a minor influence on the tau-MT interaction, whereas the presence of a C-terminal pseudorepeat region (PRR) greatly increased MT binding by a greater-than-sixfold reduction of the dissociation rate. Bioinformatic analysis revealed that the PRR contained a highly conserved motif of 18 amino acids. Disease-associated tau mutations in the PRR (K369I, G389R) did not influence apparent MT binding but increased its dynamicity. Simulation of disease-like tau hyperphosphorylation dramatically diminished the tau-MT interaction by a greater-than-fivefold decrease of the association rate with no major change in the dissociation rate. Apparent binding of tau to MTs was similar in axons and dendrites but more sensitive to increased phosphorylation in axons. Our data indicate that under the conditions of high MT density that prevail in the axon, tau's MT binding and localization are crucially affected by the presence of the PRR and tau hyperphosphorylation.
ISSN: 10591524
DOI: 10.1091/mbc.E16-06-0402

Show full item record

Page view(s)

2
Last Week
0
Last month
0
checked on Feb 23, 2024

Google ScholarTM

Check

Altmetric