Research seminars The TMEM16 /Anoctamin Protein Family: functionally diverse and implicated in Genetic Diseases

Abstract

In mammals, the family of TMEM16 proteins, also known as Anoctamins, comprises 10 members that are functionally split into Ca²⁺-activated chloride channels and Ca²⁺-dependent phospholipid scramblases. TMEM16A and TMEM16B serve as classical Ca²⁺-activated chloride channels (CaCCs) located in the plasma membrane mainly of epithelial and neuronal cell types, respectively. In particular, TMEM16B fine-tunes neuronal firing activity and contributes to sensory transduction in different olfactory systems and also in specific central neurons. While all other family members have not been fully characterized, they are believed to function as phospholipid scramblases. Scrambling activity consists in the calcium-dependent transfer of phospholipids between the leaflets of the membrane bilayer disrupting the normally asymmetrical lipid arrangement. In addition, the lipid scramblases TMEM16C through TMEM16F were also shown to mediate calcium-activated non-selective ionic currents. Many human TMEM16 proteins have been linked to genetic disorders. For instance, mutations in TMEM16C/Ano3 causes craniocervical dystonia and parkinsonism, while mutations in TMEM16E/Ano5 are associated with skeletal gnathodiaphyseal dysplasia (GDD) and muscular dystrophy. In my talk, I will address both the physiological function of TMEM16B and the effects of human TMEM16E variants causing genetic diseases.