Calcium ion (Ca2+) acts as an intracellular second messenger in living cells. Changes in cytosolic Ca2+ levels influence most fundamental cellular processes. Local and rapid changes in cytosolic Ca2+ are evoked by activation of plasma membrane voltage-gated Ca2+ channels in response to membrane depolarization. Global changes in cytosolic Ca2+ are supported by intracellular Ca2+ release channels: the inositol (1,4,5)-trisphosphate receptor (InsP3R) and the ryanodine receptor (RyanR). The functional properties and modulation of intracellular Ca2+ release channels and voltage-gated Ca2+ channels is in the focus of our research.
InsP3R is activated in response to the generation of a second messenger inositol (1,4,5)-trisphosphate (InsP3). By using molecular, biochemcial, imaging and electrophysiological methods we planar we study functional properties and modulation of InsP3 receptors (InsP3R). More recently we became interested in connection between deranged calcium signaling mediated by InsP3R and neurodegenerative diseases (Huntington’s disease, ataxias, Alzhimer’s disease).
In nervous system secretion of neurotransmitter is triggered by Ca2+ influx via presynaptic voltage-gated Ca2+ channels. Synaptic transmission is strongly affected by changes in behavior of these channels. In collaboration with Tom Sudhof’s laboratory we demonstrated specific association of carboxy-terminal region of presynaptic voltage-gated Ca2+ channels with modular adaptor proteins in biochemical experiments. Our present aim is to determine the role of discovered interactions for synaptic function. Molecular, imaging and electrophysiological experiments with primary neuronal cultures are conducted to address these questions.
RESEARCH INTERESTS
Calcium signaling
Neurodegeneration
Calcium channels and synaptic function
Huntingtons disease
Alzheimers disease
RECENT PUBLICATIONS
Hua Zhang, Anton Maximov, Yu Fu, Fang Xu, Tie-Shan Tang, Tatiana Tkatch, D. James Surmeier and Ilya Bezprozvanny, "Association of CaV1.3 L-type calcium channels with Shank" Journal of Neuroscience, 25:1037-1049, 2005
Tie-Shan Tang, Elizabeth Slow, Vitalie Lupu, Irina G. Stavrovskaya, Mutsuyuki Sugimori, Rodolfo Llinas, Bruce S. Kristal, Michael R. Hayden and Ilya Bezprozvanny, "Disturbed Ca2+ signaling and apoptosis of medium spiny neurons in Huntington's disease." Proceedings of the National Academy of Sciences (USA), 102:2602-2607, 2005
Ilya Bezprozvanny, "The inositol 1,4,5-trisphosphate receptors" Cell Calcium, 38:261-272, 2005
Zhang H, Fu Y, Altier C, Platzer J, Surmeier DJ, Bezprozvanny I, "Ca1.2 and CaV1.3 neuronal L-type calcium channels: differential targeting and signaling to pCREB." Eur J Neurosci, 23(9):2297-310, May 2006
Tu H, Nelson O, Bezprozvanny A, Wang Z, Lee SF, Hao YH, Serneels L, De Strooper B, Yu G, Bezprozvanny I, "Presenilins form ER Ca2+ leak channels, a function disrupted by familial Alzheimer’s disease-linked mutations." Cell, 126(5):981-93, September 2006
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