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P. Koulen, H. Xin, S.-Y. Hwang; Control of Inositol 1, 4, 5-Trisphosphate Receptor Mediated Calcium Signaling by Beta-Actin in Mouse Retina Ganglion Cells. Invest. Ophthalmol. Vis. Sci. 2010;51(13):1881.
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© ARVO (1962-2015); The Authors (2016-present)
Inositol-1, 4, 5-triphosphate receptors (IP3Rs) are intracellular Ca2+ channels known to be involved in several intracellular signaling pathways. IP3R mediated changes in cytosolic Ca2+ concentrations control neuronal functions ranging from synaptic transmission to differentiation and apoptosis and interface with components of the cytoskeleton. Similarly, retinal ganglion cell physiology and pathophysiology is determined by cytosolic Ca2+ transients. Determining the function of biophysically distinct IP3Rs and their control by beta-actin in retina ganglion cells provides necessary information on the molecular substrates of IP3R mediated Ca2+ signaling in these interneurons that are affected by retinopathies.
The expression and distribution of IP3Rs, beta-actin and related signaling molecules was determined with immunochemistry. Functional effects of the pharmacologic and molecular biological modulation of IP3Rs and beta-actin were analyzed with optical imaging of intracellular Ca2+ concentrations and single channel electrophysiology in mouse retinal ganglion cells.
Beta-actin and IP3Rs were colocalized intracellularly in retina ganglion cells. Binding of beta-actin to the cytosolic face of the IP3Rs significantly potentiated IP3Rs single channel activity. In and in parallel a IP3R channel. In isolated retinal ganglion cells, pharmacologic inhibition or molecular biological downregulation of beta-actin expression led to an attenuation of IP3R-mediated intracellular Ca2+ signals that showed a significant correlation with the beta-actin dependent changes in the biophysical properties of IP3Rs.
Data from the present study suggest that components of the cytoskeleton control the intracellular Ca2+ concentration in retinal neurons through direct interaction with IP3Rs. Furthermore, these components of the cytoskeleton appear capable of influencing the gain and sensitivity of Ca2+ signaling pathways indicating potential roles in retina physiology, pathophysiology and neuroprotection.
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