A novel calcium-binding protein is associated with tau proteins in tauopathy.
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.
Vega
Irving E
IE
Department of Biology, University of Puerto Rico-Rio Piedras Campus, San Juan, Puerto Rico. irving_vega@uprrp.edu
Traverso
Edwin E
EE
Ferrer-Acosta
Yancy
Y
Matos
Eduardo
E
Colon
Migdalisel
M
Gonzalez
John
J
Dickson
Dennis
D
Hutton
Michael
M
Lewis
Jada
J
Yen
Shu H
SH
D000375:Aging / Q000378:metabolism / Q000473:pathology; D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000502:physiology; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D004195:Disease Models, Animal; D020832:EF Hand Motifs / Q000502:physiology; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D024801:Tauopathies / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D016875:tau Proteins / Q000378:metabolism*
D002135:Calcium-Binding Proteins; C530752:EFHD2 protein, mouse; D016875:tau Proteins; D002118:Calcium