A novel calcium-binding protein is associated with tau proteins in tauopathy

Irving E. Vega, Edwin E. Traverso, Yancy Ferrer-Acosta, Eduardo Matos, Migdalisel Colon, John Gonzalez, Dennis W Dickson, Michael Hutton, Jada Lewis, Shu H. Yen

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

Tauopathies are a group of neurological disorders characterized by the presence of intraneuronal hyperphosphorylated and filamentous tau. Mutations in the tau gene have been found in kindred with tauopathy. The expression of the human tau mutant in transgenic mice induced neurodegeneration, indicating that tau plays a central pathological role. However, the molecular mechanism leading to tau-mediated neurodegeneration is poorly understood. To gain insights into the role that tau plays in neurodegeneration, human tau proteins were immunoprecipitated from brain lysates of the tauopathy mouse model JNPL3, which develops neurodegeneration in age-dependent manner. In the present work, a novel EF-hand domain-containing protein was found associated with tau proteins in brain lysate of 12-month-old JNPL3 mice. The association between tau proteins and the novel identified protein appears to be induced by the neurodegeneration process as these two proteins were not found associated in young JNPL3 mice. Consistently, the novel protein co-purified with the pathological sarkosyl insoluble tau in terminally ill JNPL3 mice. Calcium-binding assays demonstrated that this protein binds calcium effectively. Finally, the association between tau and the novel calcium-binding protein is conserved in human and enriched in Alzheimer's disease brain. Taken together, the identification of a novel calcium-binding protein associated with tau protein in terminally ill tauopathy mouse model and its confirmation in human brain lysate suggests that this association may play an important physiological and/or pathological role.

Original languageEnglish (US)
Pages (from-to)96-106
Number of pages11
JournalJournal of Neurochemistry
Volume106
Issue number1
DOIs
StatePublished - Jul 2008

Fingerprint

Tauopathies
tau Proteins
Calcium-Binding Proteins
Brain
Terminally Ill
Association reactions
Proteins
Calcium
EF Hand Motifs
Nervous System Diseases
Transgenic Mice
Assays
Alzheimer Disease
Genes
Mutation

Keywords

  • Alzheimer's disease
  • Calcium
  • EF-hand domain
  • Tau
  • Tauopathy

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

Vega, I. E., Traverso, E. E., Ferrer-Acosta, Y., Matos, E., Colon, M., Gonzalez, J., ... Yen, S. H. (2008). A novel calcium-binding protein is associated with tau proteins in tauopathy. Journal of Neurochemistry, 106(1), 96-106. https://doi.org/10.1111/j.1471-4159.2008.05339.x

A novel calcium-binding protein is associated with tau proteins in tauopathy. / Vega, Irving E.; Traverso, Edwin E.; Ferrer-Acosta, Yancy; Matos, Eduardo; Colon, Migdalisel; Gonzalez, John; Dickson, Dennis W; Hutton, Michael; Lewis, Jada; Yen, Shu H.

In: Journal of Neurochemistry, Vol. 106, No. 1, 07.2008, p. 96-106.

Research output: Contribution to journalArticle

Vega, IE, Traverso, EE, Ferrer-Acosta, Y, Matos, E, Colon, M, Gonzalez, J, Dickson, DW, Hutton, M, Lewis, J & Yen, SH 2008, 'A novel calcium-binding protein is associated with tau proteins in tauopathy', Journal of Neurochemistry, vol. 106, no. 1, pp. 96-106. https://doi.org/10.1111/j.1471-4159.2008.05339.x
Vega IE, Traverso EE, Ferrer-Acosta Y, Matos E, Colon M, Gonzalez J et al. A novel calcium-binding protein is associated with tau proteins in tauopathy. Journal of Neurochemistry. 2008 Jul;106(1):96-106. https://doi.org/10.1111/j.1471-4159.2008.05339.x
Vega, Irving E. ; Traverso, Edwin E. ; Ferrer-Acosta, Yancy ; Matos, Eduardo ; Colon, Migdalisel ; Gonzalez, John ; Dickson, Dennis W ; Hutton, Michael ; Lewis, Jada ; Yen, Shu H. / A novel calcium-binding protein is associated with tau proteins in tauopathy. In: Journal of Neurochemistry. 2008 ; Vol. 106, No. 1. pp. 96-106.
@article{435ee92a0e8f4f3a82dfc8526f6a8624,
title = "A novel calcium-binding protein is associated with tau proteins in tauopathy",
abstract = "Tauopathies are a group of neurological disorders characterized by the presence of intraneuronal hyperphosphorylated and filamentous tau. Mutations in the tau gene have been found in kindred with tauopathy. The expression of the human tau mutant in transgenic mice induced neurodegeneration, indicating that tau plays a central pathological role. However, the molecular mechanism leading to tau-mediated neurodegeneration is poorly understood. To gain insights into the role that tau plays in neurodegeneration, human tau proteins were immunoprecipitated from brain lysates of the tauopathy mouse model JNPL3, which develops neurodegeneration in age-dependent manner. In the present work, a novel EF-hand domain-containing protein was found associated with tau proteins in brain lysate of 12-month-old JNPL3 mice. The association between tau proteins and the novel identified protein appears to be induced by the neurodegeneration process as these two proteins were not found associated in young JNPL3 mice. Consistently, the novel protein co-purified with the pathological sarkosyl insoluble tau in terminally ill JNPL3 mice. Calcium-binding assays demonstrated that this protein binds calcium effectively. Finally, the association between tau and the novel calcium-binding protein is conserved in human and enriched in Alzheimer's disease brain. Taken together, the identification of a novel calcium-binding protein associated with tau protein in terminally ill tauopathy mouse model and its confirmation in human brain lysate suggests that this association may play an important physiological and/or pathological role.",
keywords = "Alzheimer's disease, Calcium, EF-hand domain, Tau, Tauopathy",
author = "Vega, {Irving E.} and Traverso, {Edwin E.} and Yancy Ferrer-Acosta and Eduardo Matos and Migdalisel Colon and John Gonzalez and Dickson, {Dennis W} and Michael Hutton and Jada Lewis and Yen, {Shu H.}",
year = "2008",
month = "7",
doi = "10.1111/j.1471-4159.2008.05339.x",
language = "English (US)",
volume = "106",
pages = "96--106",
journal = "Journal of Neurochemistry",
issn = "0022-3042",
publisher = "Wiley-Blackwell",
number = "1",

}

TY - JOUR

T1 - A novel calcium-binding protein is associated with tau proteins in tauopathy

AU - Vega, Irving E.

AU - Traverso, Edwin E.

AU - Ferrer-Acosta, Yancy

AU - Matos, Eduardo

AU - Colon, Migdalisel

AU - Gonzalez, John

AU - Dickson, Dennis W

AU - Hutton, Michael

AU - Lewis, Jada

AU - Yen, Shu H.

PY - 2008/7

Y1 - 2008/7

N2 - Tauopathies are a group of neurological disorders characterized by the presence of intraneuronal hyperphosphorylated and filamentous tau. Mutations in the tau gene have been found in kindred with tauopathy. The expression of the human tau mutant in transgenic mice induced neurodegeneration, indicating that tau plays a central pathological role. However, the molecular mechanism leading to tau-mediated neurodegeneration is poorly understood. To gain insights into the role that tau plays in neurodegeneration, human tau proteins were immunoprecipitated from brain lysates of the tauopathy mouse model JNPL3, which develops neurodegeneration in age-dependent manner. In the present work, a novel EF-hand domain-containing protein was found associated with tau proteins in brain lysate of 12-month-old JNPL3 mice. The association between tau proteins and the novel identified protein appears to be induced by the neurodegeneration process as these two proteins were not found associated in young JNPL3 mice. Consistently, the novel protein co-purified with the pathological sarkosyl insoluble tau in terminally ill JNPL3 mice. Calcium-binding assays demonstrated that this protein binds calcium effectively. Finally, the association between tau and the novel calcium-binding protein is conserved in human and enriched in Alzheimer's disease brain. Taken together, the identification of a novel calcium-binding protein associated with tau protein in terminally ill tauopathy mouse model and its confirmation in human brain lysate suggests that this association may play an important physiological and/or pathological role.

AB - Tauopathies are a group of neurological disorders characterized by the presence of intraneuronal hyperphosphorylated and filamentous tau. Mutations in the tau gene have been found in kindred with tauopathy. The expression of the human tau mutant in transgenic mice induced neurodegeneration, indicating that tau plays a central pathological role. However, the molecular mechanism leading to tau-mediated neurodegeneration is poorly understood. To gain insights into the role that tau plays in neurodegeneration, human tau proteins were immunoprecipitated from brain lysates of the tauopathy mouse model JNPL3, which develops neurodegeneration in age-dependent manner. In the present work, a novel EF-hand domain-containing protein was found associated with tau proteins in brain lysate of 12-month-old JNPL3 mice. The association between tau proteins and the novel identified protein appears to be induced by the neurodegeneration process as these two proteins were not found associated in young JNPL3 mice. Consistently, the novel protein co-purified with the pathological sarkosyl insoluble tau in terminally ill JNPL3 mice. Calcium-binding assays demonstrated that this protein binds calcium effectively. Finally, the association between tau and the novel calcium-binding protein is conserved in human and enriched in Alzheimer's disease brain. Taken together, the identification of a novel calcium-binding protein associated with tau protein in terminally ill tauopathy mouse model and its confirmation in human brain lysate suggests that this association may play an important physiological and/or pathological role.

KW - Alzheimer's disease

KW - Calcium

KW - EF-hand domain

KW - Tau

KW - Tauopathy

UR - http://www.scopus.com/inward/record.url?scp=45249099292&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=45249099292&partnerID=8YFLogxK

U2 - 10.1111/j.1471-4159.2008.05339.x

DO - 10.1111/j.1471-4159.2008.05339.x

M3 - Article

C2 - 18346207

AN - SCOPUS:45249099292

VL - 106

SP - 96

EP - 106

JO - Journal of Neurochemistry

JF - Journal of Neurochemistry

SN - 0022-3042

IS - 1

ER -