Heterologous expression of polycystin-1 inhibits endoplasmic reticulum calcium leak in stably transfected MDCK cells
| Autor: | Michael Sutters, Eun Kyung Lee, Roy C. Ziegelstein, Sabina Lindley, Kimberly H. Weber, Gregory G. Germino, Uma Basavanna |
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| Rok vydání: | 2008 |
| Předmět: |
medicine.medical_specialty
TRPP Cation Channels Thapsigargin Physiology Gene Expression chemistry.chemical_element Calcium Biology Endoplasmic Reticulum Kidney Transfection Calcium in biology chemistry.chemical_compound Dogs Internal medicine medicine Animals Homeostasis Humans Enzyme Inhibitors Cells Cultured Calcium signaling Ionophores Voltage-dependent calcium channel Ryanodine receptor Ionomycin Endoplasmic reticulum Cell Membrane Polycystic Kidney Autosomal Dominant Cell biology Calcium ATPase Endocrinology chemistry |
| Zdroj: | American Journal of Physiology-Renal Physiology. 294:F1279-F1286 |
| ISSN: | 1522-1466 1931-857X |
| Popis: | We previously found that polycystin-1 accelerated the decay of ligand-activated cytoplasmic calcium transients through enhanced reuptake of calcium into the endoplasmic reticulum (ER; Hooper KM, Boletta A, Germino GG, Hu Q, Ziegelstein RC, Sutters M. Am J Physiol Renal Physiol 289: F521–F530, 2005). Calcium flux across the ER membrane is determined by the balance of active uptake and passive leak. In the present study, we show that polycystin-1 inhibited calcium leak across the ER membrane, an effect that would explain the capacity of this protein to accelerate clearance of calcium from the cytoplasm following a calcium release response. Calcium leak was detected by measurement of the accumulation of calcium in the cytoplasm following treatment with thapsigargin. Heterologous polycystin-1, stably expressed in Madin-Darby canine kidney cells, attenuated the thapsigargin-induced calcium peak with no effect on basal calcium stores, mitochondrial calcium uptake, or extrusion of calcium across the plasma membrane. The capacity of polycystin-1 to limit the rate of decay of ER luminal calcium following inhibition of the pump was shown indirectly using the calcium ionophore ionomycin, and directly by loading the ER with a low-affinity calcium indicator. We conclude that disruption of ER luminal calcium homeostasis may contribute to the cyst phenotype in autosomal dominant polycystic kidney disease. |
| Databáze: | OpenAIRE |
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