Increase in tau tyrosine phosphorylation correlates with the formation of tau aggregates

Irving E Vega; Li Cui; Josh A Propst; Michael L Hutton; Gloria Lee; Shu-Hui Yen

doi:10.1016/j.molbrainres.2005.04.015

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Increase in tau tyrosine phosphorylation correlates with the formation of tau aggregates

Journal article

Peer reviewed

Increase in tau tyrosine phosphorylation correlates with the formation of tau aggregates

Irving E Vega, Li Cui, Josh A Propst, Michael L Hutton, Gloria Lee and Shu-Hui Yen

Brain research. Molecular brain research, Vol.138(2), pp.135-144

2005

DOI: 10.1016/j.molbrainres.2005.04.015

PMCID: PMC3677942

PMID: 15913839

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https://www.ncbi.nlm.nih.gov/pmc/articles/3677942View

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Abstract

Tauopathies are neurodegenerative disorders characterized by aberrant intracellular aggregation of hyperphosphorylated tau. It has been shown that aggregated tau is phosphorylated at serine, threonine, and tyrosine residues. However, the occurrence of tyrosine phosphorylation on tau proteins at different states of tau aggregation has not been shown. In this report, we utilized the tauopathy mouse model JNPL3 that expresses human 0N4R tau isoform bearing the missense P301L mutation to study the occurrence of tau tyrosine phosphorylation in the course of the development of tau aggregation. These mice develop behavioral and motor deficits and form sarkosyl-insoluble hyperphosphorylated tau in an age-dependent manner. Mass spectrometry analyses of immunopurified brain tau proteins from JNPL3 and Alzheimer's disease affected individual uncovered novel tau tyrosine-phosphorylated sites. Further studies demonstrated that the abundance of tyrosine-phosphorylated tau increases in an age-dependent manner in JNPL3 mice. Tyrosine-phosphorylated tau was detected in both soluble and sarkosyl-insoluble preparations derived from brain and spinal cord, and localized in neurons containing aggregated tau. The phosphorylation of tyrosine residues in tau appeared to occur along with that of serine and threonine residues and was not detectable in non-transgenic littermates and transgenic mice expressing 0N4R wild-type human tau. The results suggest that tyrosine phosphorylation is as important as phosphorylation of other residues in tauopathy.

Tau

Tauopathy

Tyrosine phosphorylation

Transgenic mice

Details

Title: Subtitle: Increase in tau tyrosine phosphorylation correlates with the formation of tau aggregates
Creators: Irving E Vega - Department of Neuroscience, Mayo Clinic College of Medicine, Mayo Clinic Jacksonville, Birdsall Medical Research Bldg., 4500 San Pablo Road, Jacksonville, FL 32224, USA
Li Cui - Department of Neuroscience, Mayo Clinic College of Medicine, Mayo Clinic Jacksonville, Birdsall Medical Research Bldg., 4500 San Pablo Road, Jacksonville, FL 32224, USA
Josh A Propst - Department of Neuroscience, Mayo Clinic College of Medicine, Mayo Clinic Jacksonville, Birdsall Medical Research Bldg., 4500 San Pablo Road, Jacksonville, FL 32224, USA
Michael L Hutton - Department of Neuroscience, Mayo Clinic College of Medicine, Mayo Clinic Jacksonville, Birdsall Medical Research Bldg., 4500 San Pablo Road, Jacksonville, FL 32224, USA
Gloria Lee - Department of Internal Medicine, University of Iowa School of Medicine, Iowa City, IA 52242, USA
Shu-Hui Yen - Department of Neuroscience, Mayo Clinic College of Medicine, Mayo Clinic Jacksonville, Birdsall Medical Research Bldg., 4500 San Pablo Road, Jacksonville, FL 32224, USA
Resource Type: Journal article
Publication Details: Brain research. Molecular brain research, Vol.138(2), pp.135-144
DOI: 10.1016/j.molbrainres.2005.04.015
PMID: 15913839
PMCID: PMC3677942
NLM abbreviation: Brain Res Mol Brain Res
ISSN: 0169-328X
eISSN: 1872-6941
Publisher: Elsevier B.V
Language: English
Date published: 2005
Academic Unit: Iowa Neuroscience Institute; Immunology; Internal Medicine
Record Identifier: 9984065486802771

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