Chloride intracellular channel protein 5 is a
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...
that in humans is encoded by the ''CLIC5''
gene
In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...
.
Expression and localization
CLIC5 exists in two
alternative splice variants, a smaller CLIC5A and larger CLIC5B protein.
CLIC5A is expressed chiefly in the renal
glomerulus
''Glomerulus'' () is a common term used in anatomy to describe globular structures of entwined vessels, fibers, or neurons. ''Glomerulus'' is the diminutive of the Latin ''glomus'', meaning "ball of yarn".
''Glomerulus'' may refer to:
* the filter ...
, specifically in
podocytes. Within the cell, CLIC5A is localized to the
plasma membrane and the
cytosol
The cytosol, also known as cytoplasmic matrix or groundplasm, is one of the liquids found inside cells ( intracellular fluid (ICF)). It is separated into compartments by membranes. For example, the mitochondrial matrix separates the mitochondri ...
, and associates and is regulated by the
actin
Actin is a family of globular multi-functional proteins that form microfilaments in the cytoskeleton, and the thin filaments in muscle fibrils. It is found in essentially all eukaryotic cells, where it may be present at a concentration of ov ...
cytoskeleton
The cytoskeleton is a complex, dynamic network of interlinking protein filaments present in the cytoplasm of all cells, including those of bacteria and archaea. In eukaryotes, it extends from the cell nucleus to the cell membrane and is com ...
.
CLIC5A can form ion channels in vitro and its channel activity is regulated by
actin
Actin is a family of globular multi-functional proteins that form microfilaments in the cytoskeleton, and the thin filaments in muscle fibrils. It is found in essentially all eukaryotic cells, where it may be present at a concentration of ov ...
, though measurement of its chloride conductance ''in vitro'' suggests that CLIC5A is equally selective for cations and anions. Even so, the function of CLICs as bona fide ion channels is controversial and has been disputed.
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 GTPase
Small GTPases (), also known as small G-proteins, are a family of hydrolase enzymes that can bind and hydrolyze guanosine triphosphate (GTP). They are a type of G-protein found in the cytosol that are homologous to the alpha subunit of heterotr ...
Rac1, induces the phosphorylation of
ezrin
Ezrin also known as cytovillin or villin-2 is a protein that in humans is encoded by the ''EZR'' gene.
Structure
The N-terminus of ezrin contains a FERM domain which is further subdivided into three subdomains. The C-terminus contain an ERM d ...
-moeisin-radixin (ERM) proteins and localized production of the
phosphoinositide
Phosphatidylinositol (or Inositol Phospholipid) consists of a family of lipids as illustrated on the right, where red is x, blue is y, and black is z, in the context of independent variation, a class of the phosphatidylglycerides. In such molecul ...
phosphatidylinositol-4,5-bisphosphate.
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.
Clinical relevance
Two human families with loss-of-function CLIC5 mutations have been reported, with a total of 5 affected individuals. CLIC5 deficiency results in progressive hearing loss by the second decade, vestibular abnormalities, and kidney dysfunction.
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.
See also
*
Chloride channel
Chloride channels are a superfamily of poorly understood ion channels specific for chloride. These channels may conduct many different ions, but are named for chloride because its concentration ''in vivo'' is much higher than other anions. Several ...
References
Further reading
*
*
*
*
*
*
*
*
*
External links
*
*
Ion channels
{{gene-6-stub