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2014 Grants - Roberson
BIN1 and Tau Interactions Regulating Neuronal Calcium
Erik Roberson, M.D., Ph.D.
University of Alabama at Birmingham
2014 Investigator-Initiated Research Grant: Biological Underpinnings of Genetic Risk Factors in Alzheimer’s Disease
Variations in the DNA of the BIN1 (bridging integrator 1) gene – which code for the BIN1 protein – have been found to be associated with increased risk for the development of Alzheimer’s disease. However, the role of BIN1 protein in the brain, and how variations in the BIN1 gene may affect the risk of Alzheimer’s disease are not well understood.
Nerve cells use electrical signals to rapidly transmit information through the brain. These signals are crucial for the function of the nervous system and for learning and memory. Electrical signals in nerve cells are generated by the rapid opening and closing of specialized channels, which are proteins embedded in the surface of the cell. Some such channels, known as voltage-gated calcium channels (VGCCs), allow calcium to flow into the cell when they are opened by these electrical impulses. Calcium currents in nerve cells are tightly regulated and play an important role in the normal function of the brain.
Erik Roberson, M.D., Ph.D., and colleagues have obtained preliminary evidence that the BIN1 protein interacts with VGCCs through the protein tau. Tau is one of the proteins at the focus of research into Alzheimer’s disease because it is the main component of neurofibrillary tangles, one of the characteristic features of Alzheimer’s disease. For their current studies, the research team will examine the BIN1-VGCC-Tau interaction in more detail using mice that have been genetically altered to have an Alzheimer’s-like condition and different levels of tau and BIN1. They will investigate how such genetic changes affect the number and placement of VGCCs in the cell surface, as well as the electrical activity and calcium levels of nerve cells. These studies will provide new insights into the role of BIN1 in nerve cells and possibly how changes in the genetics of BIN1 may lead to brain changes associated with Alzheimer’s disease.