CLIC5
Description
The CLIC5 (chloride intracellular channel 5) is a protein-coding gene located on chromosome 6.
CLIC5, or Chloride intracellular channel protein 5, is a protein encoded by the CLIC5 gene in humans. It exists in two splice variants: a smaller CLIC5A and a larger CLIC5B. CLIC5A is predominantly expressed in the renal glomerulus, specifically in podocytes. Within the cell, it localizes to the plasma membrane and the cytosol, associating with and being regulated by the actin cytoskeleton. While CLIC5A can form ion channels in vitro, its channel activity is regulated by actin. However, its chloride conductance in vitro suggests equal selectivity for cations and anions. The function of CLICs as bona fide ion channels remains controversial. Despite the initial belief that CLIC proteins are involved in ion transport within subcellular compartments, their actual roles extend beyond ion transport. CLIC5A, through interactions with Rac1, induces the phosphorylation of ERM proteins and localized production of phosphatidylinositol-4,5-bisphosphate. These events activate ezrin, enabling it to couple transmembrane proteins to the actin cytoskeleton, potentially contributing to the formation of podocyte foot processes involved in renal filtration. Two families with loss-of-function CLIC5 mutations have been reported, affecting a total of 5 individuals.
CLIC5 is essential for normal hearing, playing a role in the formation of stereocilia in the inner ear and the development of the organ of Corti. It can insert into membranes and form poorly selective ion channels that may also transport chloride ions. CLIC5 may contribute to the regulation of transepithelial ion absorption and secretion. Additionally, it is crucial for the development and/or maintenance of the proper glomerular endothelial cell and podocyte architecture. CLIC5 also participates in the formation of the lens suture in the eye, contributing to the normal optical properties of the lens.
CLIC5 is also known as DFNB102, DFNB103, MST130, MSTP130.
