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Anoctamins (anion channels with 8 transmembrane domains [ANO]), also known as transmembrane proteins with 16 domains (TMEM16), are highly conserved intracellular calcium (Ca2+)–activated proteins with multiple cellular functions. The ANO/TMEM16 family includes 10 members (ANO1/TMEM16A to ANO10/TMEM16K), with distinct distributions in tissues. Some of these proteins, such as ANO1 and ANO2, are prototypical Ca2+-activated chloride (Cl−) channels. Others, including ANO6, mediate Ca2+-dependent exposure of phospholipids that are normally expressed in the inner leaflet of the membrane to the extracellular surface; this process is called phospholipid scrambling or scramblase activity. Anoctamins are involved in regulation of neuronal cell excitability, epithelial secretion, smooth muscle contraction, repair of skeletal muscle membrane, and tumorigenesis. The structure, mechanism of activation, and functions of anoctamins have been reviewed recently.1–6 Anoctamins contribute to heat-induced pain7,8 and modulate excitability in neurons in the dorsal root ganglia (DRG),9 hippocampus,10 and cerebellum.11 Mutations affecting different anoctamins have been linked to several neurologic disorders, including muscle disease,12–15 cerebellar ataxia,16–18 and dystonia.19,20 Thus, anoctamins constitute a potential therapeutic target in a wide range of neurologic disorders.
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- © 2017 American Academy of Neurology
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