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Ca(2+)-activated Cl(-) channels (CaCCs) are exceptionally well adapted to subserve diverse physiological roles, from epithelial fluid transport to sensory transduction, because their gating is cooperatively controlled by the interplay between ionotropic and metabotropic signals. A molecular understanding of the dual regulation of CaCCs by voltage and Ca(2+)(More)
Dendritic spines undergo actin-based growth and shrinkage during synaptic plasticity, in which the actin depolymerizing factor (ADF)/cofilin family of actin-associated proteins are important. Elevated ADF/cofilin activities often lead to reduced spine size and immature spine morphology but can also enhance synaptic potentiation in some cases. Thus,(More)
RATIONALE Ca2+ -activated Cl channels play pivotal roles in the cardiovascular system. They regulate vascular smooth muscle tone and participate in cardiac action potential repolarization in some species. Ca2+ -activated Cl channels were recently discovered to be encoded by members of the anoctamin (Ano, also called Tmem16) superfamily, but the mechanisms(More)
Ca(2+)-binding protein-1 (CaBP1) and calmodulin (CaM) are highly related Ca(2+)-binding proteins that directly interact with, and yet differentially regulate, voltage-gated Ca(2+) channels. Whereas CaM enhances inactivation of Ca(2+) currents through Ca(v)1.2 (L-type) Ca(2+) channels, CaBP1 completely prevents this process. How CaBP1 and CaM mediate such(More)
This article reviews the current state of knowledge about the bestrophins, a newly identified family of proteins that can function both as Cl(-) channels and as regulators of voltage-gated Ca(2+) channels. The founding member, human bestrophin-1 (hBest1), was identified as the gene responsible for a dominantly inherited, juvenile-onset form of macular(More)
The Ca(2+)-activated Cl channel anoctamin-1 (Ano1; Tmem16A) plays a variety of physiological roles, including epithelial fluid secretion. Ano1 is activated by increases in intracellular Ca(2+), but there is uncertainty whether Ca(2+) binds directly to Ano1 or whether phosphorylation or additional Ca(2+)-binding subunits like calmodulin (CaM) are required.(More)
Anion transport by the colonic mucosa maintains the hydration and pH of the colonic lumen, and its disruption causes a variety of diarrheal diseases. Cholinergic agonists raise cytosolic Ca2+ levels and stimulate anion secretion, but the mechanisms underlying this effect remain unclear. Cholinergic stimulation of anion secretion may occur via activation of(More)
Bestrophins (VMD2, VMD2L1, VMD2L2, and VMD2L3) are a new family of anion channels. The mechanisms of their regulation are not yet well understood. Recently, we found that a domain (amino acids 356-364) in the C terminus of mouse VMD2L3 (mBest3) inhibited channel activity when it was expressed in HEK293 cells (Qu, Z., Cui, Y., and Hartzell, H. C. (2006) FEBS(More)
Mutations in the bestrophin-1 (Best1) gene are linked to several kinds of macular degeneration in both humans and dogs. Although bestrophins have been shown clearly to be Cl(-) ion channels, it is controversial whether Cl(-) channel dysfunction can explain the diseases. It has been suggested that bestrophins are multifunctional proteins: they may regulate(More)
Ca(v)1.3 (L-type) voltage-gated Ca2+ channels have emerged as key players controlling Ca2+ signals at excitatory synapses. Compared with the more widely expressed Ca(v)1.2 L-type channel, relatively little is known about the mechanisms that regulate Ca(v)1.3 channels. Here, we describe a new role for the PSD-95 (postsynaptic density-95)/Discs large/ZO-1(More)