Learn More
The cystic fibrosis transmembrane conductance regulator (CFTR) is a cAMP and protein kinase A (PKA)-regulated Cl(-) channel in the apical membrane of epithelial cells. The metabolically regulated and adenosine monophosphate-stimulated kinase (AMPK) is colocalized with CFTR and attenuates its function. However, the sites for CFTR phosphorylation and the(More)
Both stimulation of purinergic receptors by ATP and activation of the cystic fibrosis transmembrane conductance regulator (CFTR) inhibit amiloride-sensitive Na+ transport and activate Cl- secretion. These changes in ion transport may well affect cell volume. We therefore examined whether cell shrinkage or cell swelling do affect amiloride-sensitive Na+(More)
Although known for more than 20 years, the molecular identity of epithelial Ca(2+)-activated Cl(-) channels remains obscure. Previous candidate proteins did not hold initial promises, and thus, new hope is put into the recently identified family of bestrophin proteins, as they reflect many of the properties found for native channels. Mutations in the(More)
The cystic-fibrosis transmembrane conductance regulator (CFTR) functions as a cAMP-regulated Cl- channel and as a regulator of other membrane conductances. cAMP-dependent activation of CFTR inhibits epithelial Na+ channels (ENaC). The specificity of interaction between CFTR and ENaC was examined by coexpression of ENaC and ATP-binding cassette (ABC)(More)
Intestinal epithelial electrolyte secretion is activated by increase in intracellular cAMP or Ca2+ and opening of apical Cl− channels. In infants and young animals, but not in adults, Ca2+-activated chloride channels may cause secretory diarrhea during rotavirus infection. While detailed knowledge exists concerning the contribution of cAMP-activated cystic(More)
The cystic fibrosis transmembrane conductance regulator (CFTR) is a protein kinase A and ATP-regulated Cl- channel that also controls the activity of other membrane transport proteins, such as the epithelial Na+ channel ENaC. Previous studies demonstrated that cytosolic domains of ENaC are critical for down-regulation of ENaC by CFTR, whereas others(More)
Proteins of the bestrophin family produce Ca(2+)-activated Cl(-) currents and regulate voltage-gated Ca(2+) channels. Bestrophin 1 was first identified in the retinal pigment epithelium. Four human paralogs (hBest1-hBest4) exist, and for some bestrophins, dimeric and heterotetrameric structures have been proposed. Here, we demonstrate that hBest1-hBest4(More)
Regulator of G protein signaling (RGS) proteins function as GTPase-activating proteins (GAPs) that stimulate the inactivation of heterotrimeric G proteins. We have recently shown that RGS proteins may be regulated on a post-translational level (Benzing, T., Brandes, R., Sellin, L., Schermer, B., Lecker, S., Walz, G., and Kim, E. (1999) Nat. Med. 5,(More)
Bestrophins form Ca(2+)-activated Cl(-) channels and regulate intracellular Ca(2+) signaling. We demonstrate that bestrophin 1 is localized in the endoplasmic reticulum (ER), where it interacts with stromal interacting molecule 1, the ER-Ca(2+) sensor. Intracellular Ca(2+) transients elicited by stimulation of purinergic P2Y(2) receptors in HEK293 cells(More)
Anoctamin 1 (Ano1; TMEM16A) and anoctamin 2 (Ano2; TMEM16B) are novel Cl(-) channels transiently activated by an increase in intracellular Ca(2+). These channels are essential for epithelial Cl(-) secretion, smooth muscle peristalsis and olfactory signal transduction. They are central to inherited diseases and cancer and can act as heat sensors.(More)