The calcium‐binding EF‐hand in polycystin‐L is not a domain for channel activation and ensuing inactivation

FEBS Letters

Liu, Yan¹  Zhao, Wei¹  Li, Qiang¹  Chen, Xing-Zhen¹ 

[1] Department of Physiology, University of Alberta, 729 MSB, Edmonton, AB, Canada T6G 2H7

关键词: Autosomal dominant polycystic kidney disease;    Splice variant;    Cation channel;    Calcium;    Electrophysiology;    Xenopus oocyte;   

DOI  :  10.1016/S0014-5793(02)02513-9

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown