Dr Richard Tunwell
Biomedical Sciences BSc Teaching Lead
The cellular and molecular biology of intracellular calcium channels
The control of calcium release from intracellular stores in response to hormones and neurotransmitters is fundamentally responsible for the regulation of a wide variety of cell specific responses including apoptosis, exocytosis, proliferation, and muscle contraction. The inositol 1,4,5-trisphosphate gated and ryanodine sensitive classes of intracellular calcium channel have been shown to regulate both the quantal and kinetic elements of this calcium release. These two classes of channel may coexist or be segregated into discrete calcium stores, however, their structure, distribution and interactions with other regulatory proteins, many of them calcium binding, is still not clear.
In order to investigate these properties I am performing experiments which involve the use of isoform specific probes (antibodies and oligonucleotides) and the expression of chimeric intracellular channel proteins in both prokaryotic and eukaryotic cells. In particular I am currently using the cDNA of the green fluorescent protein from the jellyfish Aequorea victoria to construct chimeric inositol 1,4,5-trisphosphate gated and ryanodine sensitive channels to detect transfected cells expressing channel protein and to investigate using confocal microscopy the subcellular distribution of both the intracellular calcium channels and the associated calcium stores.
- George CH, Rogers SA, Bertrand BM, Tunwell RE, Thomas NL, Steele DS, Cox EV, Pepper C, Hazeel CJ, Claycomb C, Lai FA (2007). Alternative splicing of ryanodine receptors modulates cardiomyocyte Ca2+ signaling and susceptibility to apoptosis. Circulation Research, 100(6), 874 - 883.
- Ashworth R, Devogelaere B, Fabes J, Tunwell RE, Koh KR, De Smedt H, Patel S (2007). Molecular and functional characterization of inositol trisphosphate receptors during early zebrafish development. Journal of Biological Chemistry, 282(19), 13984 - 13993.
- Coward K, Owen H, Tunwell R, Swann K, Parrington J (2007). Phospholipid binding properties and functional characterization of a sea urchin phospholipase Cdelta in urchin and mouse eggs. Biochemical and Biophysical Research Communications, 357(4), 964 - 970.
- Cruttwell,C., Bernard,J., Hilly,M., Nicolas,V., Tunwell,R.E., Mauger,J.P. (2005)Dynamics of the inositol 1,4,5-trisphosphate receptor during polarisation of MDCK cells.Biology of the Cell 97(9),699-707
- Coward,K., Owen,H., Poustka,A.J., Hibbitt,O., Tunwell,R., Kubota,H., Swann,K., Parrington,J. (2004)Cloning of a novel phospholipase C-delta isoform from pacific purple sea urchin (Strongylocentrotus purpuratus) gametes and its expression during early embryonic development.Biochemical and Biophysical Research Communications 313(4), 894-901
- Halet,G., Tunwell,R., Parkinson,S.J., Carroll,J. (2004)Conventional PKCs regulate the temporal pattern of Ca2+ oscillations at fertilization in mouse eggs.Journal of Cell Biology 164(7), 1033-1044. ISSN: 0021-9525
- Halet,G., Tunwell,R., Carroll,J. (2003)Imaging PIP2 dynamics and PKC activation at fertilization.Journal of Physiology (London) 547P, SA44
- Tunwell,R.E., Colosetti,P., Cruttwell,C., Arsanto,J.P., Mauger,J.P., Cassio,D. (2003)The type 3 inositol 1,4,5-trisphosphate receptor is concentrated at the tight junction level in polarized MDCK cells.Journal of Cell Science 116(13), 2791-2803. ISSN: 0021-9533
- Parrington,J., Jones,M.L., Tunwell,R., Devader,C., Katan,M., Swann,K. (2003)Phospholipase C isoforms in mammalian spermatozoa: potential components of the sperm factor that causes Ca2+ release in eggs.Reproduction 123, 31-39. ISSN: 1470-1626
- Halet G, Tunwell R, Balla T, Swann K, Carroll J. (2002)The dynamics of plasma membrane PtdIns(4,5)P(2) at fertilization of mouse eggs.Journal of Cell Science 115(10), 2139-49.
- Song,G., Harding,S.E., Duchen,M.R., Tunwell,R.,O'Gara,P., Hawkins,T.E., Moss,S.E. (2002)Altered mechanical properties and intracellular calcium signaling in cardiomyocytes from annexin 6 null-mutant mice.FASEB Journal 16(6), 622-624. ISSN:0892-6638
- Song,G., Tunwell,R.E.A., Hawkins,T.E., Moss,S.E. (2002)Increased cardiac expression of the Na+/Ca2+ exchanger may be responsible for altered myocyte intracellular Ca2+ cycling in mice with targeted disruption of the annexin-6 gene.Circulation 102, 141. ISSN: 0009-7322
- Tunwell, R.E.A., & Lai, F.A (1996)Ryanodine receptor expression in the kidney and a non-excitable kidney epithelial cell.Journal of Biological Chemistry, (in press
- Tunwell, R.E.A., Wickenden, C., Bertrand B.M.A., Shevchenko, V.I., Walsh, M.B., Allen P.D. & Lai, F.A (1996)The human cardiac muscle ryanodine receptor-calcium release channel: identification, primary structure and topological analysis.Biochemical Journal 318: 477-487
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