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FRISC: The Faculty Research Interests Science Comparator |
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Assistant Professor of Physiology
Cell Regulation
Neuroscience
Office: (214) 648-6737
FAX: (214) 648-2974
Email: Ilya.Bezprozvanny@email.swmed.edu
Homepage: http://www.swmed.edu/home_pages/facultystaff/ilya
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 planar lipid bilayer in
vitro reconstitution technique, we study properties of InsP3R at the single channel
level. The main emphasis of our work is to understand how activity of these channels is
modulated in the cell. Recently, we discovered direct functional coupling between
InsP3R and lipid messenger phosphatidylinositol (4,5)-bisphosphate (PIP2). Now we focus
our efforts on understanding molecular basis and physiological significance of InsP3R-PIP2
interaction.
Several InsP3R isoforms and splice variants have been
isolated but the functional differences between different InsP3R subtypes are not known.
We set up functional expression of InsP3R in heterologous expression system and
characterize functional properties of recombinant InsP3R type I in planar lipid bilayers.
Our long-term goal is to characterize the functional differences between multiple InsP3R
isoforms and to determine structural determinants responsible for their major functional
properties. Combination of molecular techniques with single channel recordings is used to
address this set of questions.
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 Südhof'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.
Selected Publications:
A. Maximov, T.C. Südhof, I. Bezprozvanny (1999) Association of
neuronal voltage-gated calcium channels with modular adaptor proteins. The Journal of
Biological Chemistry (Communication), in press.
E. Kaznacheyeva, V. D. Lupu, I. Bezprozvanny (1998) Single-channel properties of
inositol (1,4,5)-trisphosphate receptor heterologously expressed in HEK-293 cells.
Journal
of General Physiology, v. 111, pp. 847-856.
V. D. Lupu, E. Kaznacheyeva, R. J. Falck, M. U. Krishna, I. Bezprozvanny (1998)
Functional coupling of phosphatidylinositol 4,5-bisphosphate to inositol
1,4,5-trisphosphate receptor. The Journal of Biological Chemistry (Communication),
v. 273, pp. 14067-14070.
I. Bezprozvanny, R.H. Scheller, R.W. Tsien (1995) Functional impact of syntaxin on
gating of N-type and Q-type calcium channels. Nature, vol. 378, pp. 623-626.
I. Bezprozvanny, B. Ehrlich. (1995) The inositol 1,4,5-trisphosphate (InsP3) receptor.
Journal
of Membrane Biology, vol. 145, pp. 205-216.
I. Bezprozvanny, J. Watras, B. Ehrlich. (1991) Bell-shaped calcium response curves of
Ins(1,4,5)P3- and calcium-gated channels from endoplasmic reticulum of cerebellum.
Nature,
vol. 351, pp. 751-754.
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