Study of the Ca2+-activated chloride channels and phospholipid scramblases of the TMEM16/Anoctamin family

Members of the TMEM16/Anoctamin membrane protein family in animals are functionally split into two categories: TMEM16A/Ano1 and TMEM16B/Ano2 function as Ca2+ activated chloride channels, while few others, among which TMEM16E/Ano5 and TMEM16F/Ano6, are Ca2+ dependent phospholipid scramblases mediating the transfer of phospholipids between the leaflets of the membrane bilayer, causing the regulated collapse of membrane asymmetry.
TMEM16A and TMEM16B form Ca2+ activated Cl- channels that are involved in a variety of physiological functions, such as transepithelial ion transport, olfaction, phototransduction, smooth muscle contraction, nociception, cell proliferation and control of neuronal excitability.
TMEM16s cause a variety of genetic diseases, in particular the scramblase TMEM16F/Ano6 is associated to the bleeding disorder named Scott syndrome, while the scramblase TMEM16E/Ano5 to the autosomal-dominant bone disease gnathodiaphyseal dysplasia (GDD) and two ereditary recessive forms of muscle dystrophies, limb-girdle muscular dystrophy type 2L (LGMD2L) and Miyoshi myopathy type 3 (MMD3).
My research activities include the study of
- the biophysical and pharmacological properties of the Ca2+ activated chloride channels TMEM16A and TMEM16B
- the contribution of Ca2+ activated chloride currents to the electrical activity of olfactory sensory neurons (in collaboration with Prof. Menini of SISSA, Trieste)
- the functional activity of TMEM16E/Ano5 and its roles in health and disease.

Members:
Anna Elisabetta Boccaccio (Principal investigator)
Eleonora Di Zanni
Antonella Gradogna
Cristiana Picco
Joachim Scholz - Starke