Multifaceted CFTR: novel role in ROS signaling and apoptotic cell death--a commentary on 'CFTR mediates cadmium-induced apoptosis through modulation of ROS levels in mouse proximal tubule cells'.

摘要

The cystic fibrosis transmembrane conductance regulator (CFTR) is a 1480-amino-acid protein that belongs to the ATP-binding cassette (ABC) family of integral membrane proteins. It is mainly located in the apical membrane area of secretory epithelia, where it functions as a cAMP-dependent CI- channel [1]. Mutations in the CFTR gene cause cystic fibrosis (CF), the most common autosomal recessive disease in the Caucasian population [2]. Additional roles have been attributed to CFTR, e.g., as a "conductance regulator" via autocrine signaling through CFTR-mediated release of ATP, which controls the activity of outwardly rectifying Cl~ channels, in particular those involved in volume regulation [3,4]. In addition, recent studies indicate that, similar to other members of the ABC protein family, CFTR mediates glutathione (GSH) export from cells [5]. In fact, a defect in this GSH transport function of CFTR may contribute to the pathology of CF [6]. In addition to exocrine epithelia, CFTR has been located in the mammalian kidney, particularly in the apical pole of proximal (PT) and distal tubule (DT) cells [7,8]. In the DT, CFTR mediates cAMP-dependentCl- currents in the apical membrane, but not in the PT [9,10], and so far its physiological function there has remained elusive. Moreover, despite the high level of CFTR expression in the kidney, no overwhelming renal phenotype has been associated with CF [11,12].