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.

Calcium homeostasis and signaling in the blood-stage malaria parasite.

The nature of the mechanisms underlying Ca2+ homeostasis in malaria parasites has puzzled investigators for almost two decades. This review summarizes the current knowledge about Ca2+ homeostasis in Plasmodium spp and highlights some key aspects of this process that are specific to this parasite. Plasmodium spp are exposed, during their intracellular stage, not to the usual millimolar concentrations of Ca2+ found in body fluids, but rather to the very low Ca2+ environment of the host cell cytoplasm. Two crucial questions then arise: (1) how is Ca2+ homeostasis achieved by these protozoa; and (2) do they use Ca2+-based signaling pathways? By critically reviewing the recent literature in the field, Célia Garcia here provides at least some partial answers to these questions.