International Union of Basic and Clinical Pharmacology. LXXXV: Calcium-Activated Chloride Channels

Identification of a dimerization domain in the TMEM16A calcium-activated chloride channel (CaCC)

“…Because the dimerization domain identified in our studies exhibits no homology to any other known protein according to protein BLAST algorithms, further investigation of this channel will likely reveal unique oligomerization strategies that may not have been evident from these previously described models. TMEM16A plays an important physiological role in many different cell types (2). In addition, its close homologs TMEM16B and TMEM16F have been implicated in sensory transduction and modulation of central neuronal signaling (4,5) and blood coagulation diseases (6, 7), respectively.…”

“…R ecent identification of transmembrane protein with unknown function 16 (TMEM16A) as the calcium-activated chloride channel (CaCC) first described in the frog oocyte has enabled molecular studies of this novel ion channel family (1,2). Homologs of this channel have been identified in organisms throughout the evolutionary lineage, including yeast, plants, invertebrates, and vertebrates (3).…”

Calcium-activated chloride channel ANO1 promotes breast cancer progression by activating EGFR and CAMK signaling

“…ANO1 activity regulates airway fluid secretion, gut motility, secretory functions of exocrine glands, and vascular smooth muscle contraction and recently was reported to be involved in nociception (22,23). Not surprisingly, knockout of ANO1 is embryonically lethal, and its dysregulation plays a critical role in several disease states, including pulmonary diseases, hypertension, and diarrhea (22).…”

“…ANO1 activity regulates airway fluid secretion, gut motility, secretory functions of exocrine glands, and vascular smooth muscle contraction and recently was reported to be involved in nociception (22,23). Not surprisingly, knockout of ANO1 is embryonically lethal, and its dysregulation plays a critical role in several disease states, including pulmonary diseases, hypertension, and diarrhea (22). The identification of activators and inhibitors in low molecular weight compound screens suggests that chemical modification of ANO1 function is feasible, making it a promising therapeutic target (24)(25)(26).…”

Study of permeation and blocker binding in TMEM16A calcium-activated chloride channels

“…1 At least some members of the TMEM16 (TMEM16A-K) protein family-particularly TMEM16A and TMEM16B-are known to form CaCC. 2 Functional channels have been generated from purified TMEM16 proteins by means of liposome reconstitution, indicating that no additional subunits are required. 3,4 Although the crystal structure of a TMEM16 protein has been reported, the structure of the pore of these channels is still enigmatic.…”