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
Bezprozvanny I, Mattson MP, "Neuronal calcium mishandling and the pathogenesis of Alzheimer’s disease." Trends Neurosci, 31(9):454-63, September 2008
Zhang H, Li Q, Graham RK, Slow E, Hayden MR, Bezprozvanny I, "Full length mutant huntingtin is required for altered Ca2+ signaling and apoptosis of striatal neurons in the YAC mouse model of Huntington’s disease." Neurobiol Dis, 31(1):80-8, July 2008
Zhang H, Das S, Li QZ, Dragatsis I, Repa J, Zeitlin S, Hajnoczky G, Bezprozvanny I, "Elucidating a normal function of huntingtin by functional and microarray analysis of huntingtin-null mouse embryonic fibroblasts." BMC Neurosci, 9:38, April 2008
Tang TS, Chen X, Liu J, Bezprozvanny I, "Dopaminergic signaling and striatal neurodegeneration in Huntington’s disease." J Neurosci, 27(30):7899-910, July 2007
Nelson O, Tu H, Lei T, Bentahir M, de Strooper B, Bezprozvanny I, "Familial Alzheimer disease-linked mutations specifically disrupt Ca2+ leak function of presenilin 1." J Clin Invest, 117(5):1230-9, May 2007
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