Emerging Concepts in Ion Channel Biophysics

Emerging Concepts in Ion Channel Biophysics

Poster Abstracts

53-POS Board 53 Mutations in the Polycystin Fold Cause Loss-of-function in PKD Channels Leo Ng , Thuy Vien, Paul DeCaen. Northwestern University, Chicago, IL, USA. The polycystins (PKD2 and PKD2-L1) is a class of TRP (Transient Receptor Potential) ion channels whose biophysics and function in cell biology are poorly understood. Nonetheless, several mutations in PKD2 have been determined to be causative of Autosomal dominant polycystic kidney disease (ADPKD), a common monogenetic disorder characterized by proliferative cysts which leads to renal failure in adulthood. In a collaboration, we have solved the structure of the homo-tetrameric PKD2 channel using cryo-EM. We will present electrophysiological data in conjunction with the PKD2 structure to provide insights on the specific motifs involved in gating. We drew connections with a homologous channel (PKD2-L1) and identified residues that are involved in voltage sensing and channel modulation. Emphasis was placed on the extracellular “polycystin domain” which is unique to these channels and is a hotspot for ADPKD pathogenic mutations. We also looked at co-localization of these mutants in cilia using superresolution microscopy.

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