Related Experiment Video

Updated: Sep 13, 2025

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

9.0K

Stoichiometric 14-3-3ζ binding promotes phospho-Tau microtubule dissociation and reduces aggregation and condensation

Janine Hochmair1, Maxime C M van den Oetelaar2, Leandre Ravatt1,3,4

  • 1German Center for Neurodegenerative Diseases (DZNE), Berlin, Germany.

Communications Biology
|July 31, 2025
PubMed

Insights

14-3-3ζ protein binding enhances Tau solubility and prevents its aggregation by detaching phosphorylated Tau from microtubules. This protein acts as a chaperone, crucial for brain health and preventing neurodegenerative diseases.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Biochemistry

Background:

  • Microtubule (MT) association of Tau protein decreases with phosphorylation.
  • Increased cytosolic phosphorylated Tau risks pathological aggregation, linked to neurodegenerative diseases.

Purpose of the Study:

  • To investigate the role of 14-3-3ζ in regulating Tau solubility and aggregation.
  • To elucidate the mechanisms by which 14-3-3ζ interacts with Tau.

Main Methods:

  • Investigated Tau-microtubule interactions and Tau aggregation.
  • Analyzed the effect of 14-3-3ζ binding on phosphorylated Tau.
  • Studied Tau:14-3-3ζ co-condensation dynamics.

Main Results:

  • 14-3-3ζ binding enhances cytosolic Tau solubility by promoting phosphorylated Tau removal from MTs.
  • 14-3-3ζ inhibits Tau aggregation directly and indirectly by suppressing condensate formation.
  • Site-specific binding to phosphorylated Tau (S214, S324) mediates these effects.
  • Multivalent electrostatic interactions enable phosphorylation-independent Tau:14-3-3ζ co-condensation.

Conclusions:

  • 14-3-3ζ acts as a multi-modal chaperone for Tau in the healthy brain.
  • 14-3-3ζ binding is critical for preventing Tau aggregation and mitigating neurodegenerative disease risk.

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

18.5K
In Vitro Assay for Studying the Aggregation of Tau Protein and Drug Screening09:49

In Vitro Assay for Studying the Aggregation of Tau Protein and Drug Screening

Published on: November 20, 2018

18.9K

Related Concept Videos

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...
2.1K
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...
2.8K
Drugs that Destabilize Microtubules01:10

Drugs that Destabilize Microtubules

Microtubules are dynamic structures and can be regulated by microtubule targeting agents (MTAs). Microtubule destabilizing drugs are a class of MTAs that destabilize and prevent microtubules' polymerization. Both natural and synthetic chemicals can be found under this class of drugs. Vincristine and vinblastine, two vinca alkaloids, and colchicine were among the first to be discovered. These drugs can affect cells in various ways, either by inducing a change in cell morphology, preventing...
2.0K
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...
5.3K
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...
4.5K