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Structure–Function of TMEM16 Ion Channels and Lipid Scramblases

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Ion Channels in Biophysics and Physiology

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1349))

Abstract

The TMEM16 protein family comprises two novel classes of structurally conserved but functionally distinct membrane transporters that function as Ca2+-dependent Cl– channels (CaCCs) or dual functional Ca2+-dependent ion channels and phospholipid scramblases. Extensive functional and structural studies have advanced our understanding of TMEM16 molecular mechanisms and physiological functions. TMEM16A and TMEM16B CaCCs control transepithelial fluid transport, smooth muscle contraction, and neuronal excitability, whereas TMEM16 phospholipid scramblases mediate the flip-flop of phospholipids across the membrane to allow phosphatidylserine externalization, which is essential in a plethora of important processes such as blood coagulation, bone development, and viral and cell fusion. In this chapter, we summarize the major methods in studying TMEM16 ion channels and scramblases and then focus on the current mechanistic understanding of TMEM16 Ca2+- and voltage-dependent channel gating as well as their ion and phospholipid permeation.

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Acknowledgments

This work was supported by grants National Institutes of Health NIH-DP2-GM126898 (to H.Y.) and the American Heart Association Pre-Doctoral Fellowship 19PRE34380456 (to S.C.L.).

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  1. Department of Biochemistry, Duke University School of Medicine, Durham, NC, USA

    Son C. Le & Huanghe Yang

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  1. Son C. Le
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  2. Huanghe Yang
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Correspondence to Huanghe Yang .

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  1. Shenzhen Bay Laboratory, Institute of Molecular Physiology / Virginia Commonwealth University School of Medicine, Shenzhen, Guangdong Province, China

    Lei Zhou

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Le, S.C., Yang, H. (2021). Structure–Function of TMEM16 Ion Channels and Lipid Scramblases. In: Zhou, L. (eds) Ion Channels in Biophysics and Physiology. Advances in Experimental Medicine and Biology, vol 1349. Springer, Singapore. https://doi.org/10.1007/978-981-16-4254-8_6

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