Polycystin-2-like protein 1
calcium-activated cation channel activity
The calcium-binding EF-hand in polycystin-L is not a domain for channel activation and ensuing inactivation.
Polycystin-L (PCL) shares high homology with polycystin-2, the product of polycystic kidney disease gene-2. It was previously shown that the PCL forms a non-selective cation channel activated by calcium influx. However, it remains unclear whether calcium activates/inactivates PCL by binding to the EF-hand motif located on the cytoplasmic carboxyl-terminus. Here we obtained two PCL splice variants from liver (PCL-LV, lacking the EF-hand) and testis (PCL-TS, lacking 45 amino acids on the carboxyl tail) using PCR-based approaches. When expressed in Xenopus oocytes and studied using electrophysiology both splice variants exhibited basal cation channel activity and calcium-induced channel activation. While PCL-TS displayed similar activation to PCL, PCL-LV exhibited a three-fold increased activation. All five PCL C-terminal artificial truncation mutants also exhibited basal and calcium-activated channel activities, in particular the mutant T622X lacking the EF-hand was associated with increased activation. Our data demonstrate that the EF-hand and other parts of the carboxyl tail of PCL are not determinants of channel activation/inactivation although the EF-hand seems to be involved in the modulation of these processes.