ANO6 Membrane Protein Introduction

Introduction of ANO6

ANO6, also known as TMEM16F, is a member of transmembrane protein 16 (TMEM16) family, which plays important roles in a variety of physiological functions, including ion transport, phospholipid scrambling and regulating other ion channels. The crystal structure of ANO6 has not been reported so far. The predicted structural model according the amino acid sequence proposes that ANO6 possesses eight predicted transmembrane helices. Meanwhile, its predicted structure reveals a pore formed by the fifth and sixth transmembrane helices, which containing a p-loop dipping back into the membrane.

Function of ANO6 Membrane Protein

ANO6 is reported to be involved in quite a variety of biological processes. It is also known as small-conductance calcium-activated nonselective cation channel because it can form an outwardly rectifying, Ca²⁺-dependent and a volume-regulated Cl⁻ channel, which is activated during apoptotic cell death. ANO6 facilitates apoptotic cell shrinkage and is a component of the ubiquitous outwardly rectifying Cl⁻ channel that has been identified in many cell types. Besides, ANO6 is reported to form an outwardly rectifying, Ca²⁺-dependent and a volume-regulated Cl⁻ channel, which is claimed to be a Ca²⁺-regulated nonselective cation channel permeable for Ca²⁺. It is shown to be essential for Ca²⁺-mediated scrambling of membrane phospholipids. ANO6 can regulate cell blebbing and microparticle shedding. The deficiency of ANO6 in blood cells of Scott patients or the ANO6 knockout mice appears to affect all of these cell responses. Furthermore, ANO6 deficiency in mice impairs the mineralization of osteoblasts, resulting in reduced skeletal development.

Fig.1 Model for the role of ANO6 in macrophages (Ousingsawat, 2015).

Application of ANO6 Membrane Protein in Literature

1. Ousingsawat J., et al. Anoctamin 6 mediates effects essential for innate immunity downstream of P2X7 receptors in macrophages. Nature Communications. 2015, 6:6245. PubMed ID: 25651887
   
   

   This article demonstrates that ANO6 is an essential component of the immune defense by macrophages. ANO6 is activated by P2X7 receptors, and then stimulates the bacterial phagocytosis and is killed by mouse and human THP-1 macrophages.

2. Kunzelmann K., et al. Molecular functions of anoctamin 6 (TMEM16F): a chloride channel, cation channel, or phospholipid scramblase? Pflügers Archiv - European Journal of Physiology. 2014, 466(3):407-414. PubMed ID: 23748496
   
   

   This article summarizes the currently available information on the diverse roles of ANO6 and its deficiency in mice impairs the mineralization of osteoblasts, resulting in reduced skeletal development. The authors of this review try to clear up some of the existing controversies about the functions of ANO6.

3. Bricogne C., et al. TMEM16F activation by Ca²⁺ triggers plasmalemma expansion and directs PD-1 trafficking. bioRxiv. 2018, 10 (1101): 227-235. PubMed ID: 24922701
   
   

   This article reports that the activation of ANO6 can trigger large-scale surface membrane expansion in parallel with lipid scrambling in Jurkat T cells and HEK293 cells, and then the cells undergo extensive membrane shedding.

4. Suzuki T., et al. Functional Swapping between Transmembrane Proteins TMEM16A and TMEM16F. The Journal of Biological Chemistry. 2014, 289(11):7438-7447. PubMed ID: 24478309
   
   

   This article indicates that TMEM16A and ANO6 use a similar mechanism for sorting to plasma membrane and protein stabilization, but their functional domains differ significantly.

5. Kmit A., et al. Calcium-activated and apoptotic phospholipid scrambling induced by Ano6 can occur independently of Ano6 ion currents. Cell Death & Disease. 2013, 4(4):e611. PubMed ID: 23618909
   
   

   This article suggests that ANO6 causes chloride and cation currents, which is required for Ca²⁺-dependent phospholipid scrambling because whole-cell currents were inhibited by siRNA knockdown of ANO6.

ANO6 Preparation Options

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Reference

1. Ousingsawat J., et al. (2015). Anoctamin 6 mediates effects essential for innate immunity downstream of P2X7 receptors in macrophages. Nature Communications. 6:6245.

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