CLIC5 exists in two alternative splice variants, a smaller CLIC5A and larger CLIC5B protein.
CLIC5A is expressed chiefly in the renal glomerulus, specifically in podocytes. Within the cell, CLIC5A is localized to the plasma membrane and the cytosol, and associates and is regulated by the actincytoskeleton.[2] CLIC5A can form ion channels in vitro and its channel activity is regulated by actin, though measurement of its chloride conductance in vitro suggests that CLIC5A is equally selective for cations and anions.
Function
Although chloride intracellular channel (CLIC) proteins were thought to be involved in ion transport in subcellular compartments, their actual functions suggest their role in diverse cellular and physiological functions including apoptosis and angiogenesis in CLIC1.
CLIC5A, through its interactions with the small GTPaseRac1, induces the phosphorylation of ezrin-moeisin-radixin (ERM) proteins and localized production of the phosphoinositide phosphatidylinositol-4,5-bisphosphate.[3] These two events activate ezrin, enabling it to couple transmembrane proteins to the actin cytoskeleton, which could represent a mechanism by which podocyte foot processes form to enable renal filtration.[4]
Clinical relevance
CLIC5A deficiency in mouse models potentiates glomerular injury in hypertension. In these mice, podocyte foot processes were also more sparse and disperse than in wild-type mice.[4]
↑Al-Momany A, Li L, Alexander RT, Ballermann BJ (December 2014). "Clustered PI(4,5)P₂ accumulation and ezrin phosphorylation in response to CLIC5A". Journal of Cell Science. 127 (Pt 24): 5164–78. doi:10.1242/jcs.147744. PMID25344252.
↑ 4.04.1Tavasoli M, Li L, Al-Momany A, Zhu LF, Adam BA, Wang Z, Ballermann BJ (April 2016). "The chloride intracellular channel 5A stimulates podocyte Rac1, protecting against hypertension-induced glomerular injury". Kidney International. 89 (4): 833–47. doi:10.1016/j.kint.2016.01.001. PMID26924049.
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