Signaling Mechanisms of TMEM16a Regulation

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The TMEM16a gene encodes for a Ca2+-activated Cl- channel that is broadly expressed in eukaryotes and plays an important role in human health and disease. TMEM16a channels are required for numerous physiologic processes, including regulation of neuronal and cardiac excitability, uterine contractility, regulation of electrolyte balance, and sensory transduction. Their importance is evidenced by the embryonic lethality of TMEM16a knockout mice, and by the association of mutations in this channel with craniofacial cancers. Aside from their Ca2+-dependent activation, it is not understood how these channels are regulated. Our lab is interested in uncovering the signaling mechanisms that modulate the activity of TMEM16a channels. Our goal is to understand the primary TMEM16a regulatory pathways, and to facilitate the development of novel therapeutic options for treating disorders caused by TMEM16a deficiencies. 1