Related Experiment Video

Updated: Jun 12, 2026

Assay for Phosphorylation and Microtubule Binding Along with Localization of Tau Protein in Colorectal Cancer Cells
12:55

Assay for Phosphorylation and Microtubule Binding Along with Localization of Tau Protein in Colorectal Cancer Cells

Published on: October 10, 2017

Microtubule destruction induces tau liberation and its subsequent phosphorylation

Tomohiro Miyasaka1, Sinji Sato, Yoshitaka Tatebayashi

  • 1Laboratory for Alzheimer's Disease, Brain Science Institute, The Institute of Physical and Chemical Research (RIKEN),Wako-shi, Saitama, Japan. tomiyasa@mail.doshisha.ac.jp

FEBS Letters
|June 22, 2010
PubMed

Insights

Microtubule (MT) disruption, not tau phosphorylation, may initiate Alzheimer's disease pathology. Studies show MT breakdown triggers tau hyperphosphorylation, suggesting a new therapeutic target for Alzheimer's disease.

Area of Science:

  • Neuroscience
  • Cell Biology
  • Pathology

Background:

  • Alzheimer's disease (AD) is characterized by neurofibrillary tangles composed of hyperphosphorylated tau protein.
  • The relationship between tau phosphorylation and microtubule (MT) disruption in AD pathogenesis remains unclear.

Purpose of the Study:

  • To investigate whether microtubule (MT) disruption can induce tau phosphorylation.
  • To elucidate the causal link between MT structure and tau pathology in Alzheimer's disease.

Main Methods:

  • Co-expression of stathmin (an MT-disrupting protein) and tau in COS-7 cells.
  • Analysis of MT structure and tau phosphorylation at specific sites (Thr-181, Ser-202, Thr-205, Thr-231).
  • Comparison with effects of c-Jun N-terminal kinase activation and phosphatase inhibition on tau phosphorylation.

Main Results:

  • Stathmin expression caused significant MT disruption (catastrophe).
  • MT disruption induced by stathmin led to hyperphosphorylation of tau at key Alzheimer's disease-associated sites.
  • c-Jun N-terminal kinase activation or phosphatase inhibition caused tau phosphorylation without affecting MT structure.

Conclusions:

  • Microtubule (MT) disruption appears to be an upstream event that induces tau hyperphosphorylation.
  • These findings suggest that preserving MT stability may be a potential therapeutic strategy for Alzheimer's disease.

More Related Videos

In Vitro Aggregation Assays Using Hyperphosphorylated Tau Protein09:22

In Vitro Aggregation Assays Using Hyperphosphorylated Tau Protein

Published on: January 2, 2015

Nuclear Magnetic Resonance Spectroscopy for the Identification of Multiple Phosphorylations of Intrinsically Disordered Proteins12:47

Nuclear Magnetic Resonance Spectroscopy for the Identification of Multiple Phosphorylations of Intrinsically Disordered Proteins

Published on: December 27, 2016

Related Concept Videos

Destabilization of Microtubules01:45

Destabilization of Microtubules

The destabilization of microtubules can occur during different stages of the microtubule lifecycle, such as nucleation or elongation. It can take place at either end of the microtubule or in the microtubule lattices as a whole. The lifespan of individual microtubules within a cell varies according to the cell type and stage of the cell cycle. During interphase, the lifespan of the microtubule is about 30 minutes, while during cell division, it is about 15 minutes. In axonal microtubules of...
Microtubule Instability02:17

Microtubule Instability

Microtubules are hollow cylindrical filaments having a diameter of approximately 25 nm and a length that varies from 200 nm to 25 μm. GTP-bound tubulin subunits form αβ-heterodimers for microtubule assembly. These core building blocks interact longitudinally, polymerizing into protofilaments. The protofilaments then interact with one another through lateral bonding forces to form stable cylindrical microtubules. These cylindrical filaments are dynamic as they undergo repeated assembly and...
Microtubule Instability02:17

Microtubule Instability

Microtubules are hollow cylindrical filaments having a diameter of approximately 25 nm and a length that varies from 200 nm to 25 μm. GTP-bound tubulin subunits form αβ-heterodimers for microtubule assembly. These core building blocks interact longitudinally, polymerizing into protofilaments. The protofilaments then interact with one another through lateral bonding forces to form stable cylindrical microtubules. These cylindrical filaments are dynamic as they undergo repeated assembly and...
Microtubule Associated Proteins (MAPs)01:42

Microtubule Associated Proteins (MAPs)

Microtubule function and architecture are regulated by an array of specialized proteins called microtubule-associated proteins or MAPs. These proteins are widespread across different organisms and have conserved protein motifs, like the multi-TOG domain for tubulin binding found in the CLASP family of MAPs. Some MAPs are lineage-specific based on their conserved domains. Their functions depend upon the cytoskeletal architecture and cell type they are located within. In-plant cells, a specific...
Drugs that Stabilize Microtubules01:15

Drugs that Stabilize Microtubules

Microtubules are dynamic structures that undergo cycles of catastrophe and rescue. The microtubules play a central role in cell division by forming the spindle apparatus for segregating the chromosomes. This makes them ideal targets for regulating dividing cells in tumors and malignant cancer cells. Microtubule stabilizing drugs help stabilize the microtubule formation and promote its polymerization. Paclitaxel was the first microtubule stabilizing agent used as anticancer drug in chemotherapy...
Phosphorylation01:02

Phosphorylation

The addition or removal of phosphate groups from proteins is the most common chemical modification that regulates cellular processes. These modifications can affect the structure, activity, stability, and localization of proteins within cells as well as their interactions with other proteins.
During phosphorylation, protein kinases transfer the terminal phosphate group of ATP to specific amino acid side chains of substrate proteins. Serine, threonine, and tyrosine are the most commonly...