Related Experiment Video
Updated: May 29, 2026
12:55
Assay for Phosphorylation and Microtubule Binding Along with Localization of Tau Protein in Colorectal Cancer Cells
Published on: October 10, 2017
Pseudohyperphosphorylation has differential effects on polymerization and function of tau isoforms.
Benjamin Combs1, Kellen Voss, T Chris Gamblin
1Molecular Biosciences, University of Kansas, Lawrence, Kansas 66045, United States.
Biochemistry
|September 28, 2011
Summary
The microtubule-associated protein tau
Area of Science:
- Neuroscience
- Molecular Biology
- Biochemistry
Background:
- The microtubule-associated protein tau (MAPT) has six isoforms generated by alternative splicing.
- Hyperphosphorylated tau aggregates in neurodegenerative diseases like Alzheimer's.
- Isoform composition of tau aggregates influences disease pathology.
Purpose of the Study:
- To investigate the differential effects of a specific pseudophosphorylation pattern (7-Phos) on all tau isoforms.
- To understand how this phosphorylation pattern influences tau's electrophoretic mobility, aggregation, and microtubule binding.
Main Methods:
- In vitro analysis of all six tau isoforms.
- Application of a pseudophosphorylation mutation pattern (7-Phos) mimicking GSK-3β phosphorylation.
- Assessment of electrophoretic mobility, aggregation propensity, and microtubule stabilization.
Main Results:
- Pseudophosphorylation (7-Phos) impacted all tau isoforms.
- Differential effects were observed, with some isoforms being more affected than others.
- These findings suggest isoform-specific conformational changes induced by hyperphosphorylation.
Conclusions:
- Hyperphosphorylation patterns can differentially affect tau isoforms.
- This differential effect may dictate the specific tau isoform composition found in disease-related aggregates.
- Understanding these isoform-specific responses is crucial for tauopathy research.
Related Concept Videos
01:02Phosphorylation
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...
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...
02:54Protein Kinases and Phosphatases
Proteins undergo chemical modifications that trigger changes in the charge, structure, and conformation of the proteins. Phosphorylation, acetylation, glycosylation, nitrosylation, ubiquitination, lipidation, methylation, and proteolysis are various protein modifications that regulate protein activity. Such modifications are usually enzyme-driven.
Protein kinases
Many proteins in the cell are regulated by phosphorylation, the addition of a phosphate group. A family of enzymes called kinases...
Protein kinases
Many proteins in the cell are regulated by phosphorylation, the addition of a phosphate group. A family of enzymes called kinases...
02:04Covalently Linked Protein Regulators
Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein.
These groups modify specific amino acids in a protein.
01:42Phosphoinositides and PIPs
Phosphoinositides are a group of phospholipids containing a glycerol backbone with two fatty acid chains and a phosphate attached to a myoinositol sugar ring. The inositol head group extends into the cytoplasm, where it is modified by adding phosphate groups to form phosphatidylinositol phosphates or PIPs.
Different phosphoinositides are synthesized and recruited on the cytosolic face of the plasma membrane. The localization of specific phosphoinositides concentrated in separate membrane...
Different phosphoinositides are synthesized and recruited on the cytosolic face of the plasma membrane. The localization of specific phosphoinositides concentrated in separate membrane...