Dystonin (DST), also known as bullous pemphigoid antigen 1 (BPAG1), isoforms 1/2/3/4/5/8, is a
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...
that in humans is encoded by the ''DST''
gene
In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...
.
This gene encodes a member of the
plakin protein family of adhesion junction plaque proteins. Multiple alternatively spliced transcript variants encoding distinct isoforms have been found for this gene, but the full-length nature of some variants has not been defined. It has been known that some isoforms are expressed in neural and muscle tissue, anchoring neural intermediate filaments to 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 ...
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 compos ...
, and some isoforms are expressed in epithelial tissue, anchoring keratin-containing
intermediate filament
Intermediate filaments (IFs) are cytoskeleton, cytoskeletal structural components found in the cells of vertebrates, and many invertebrates. Homologues of the IF protein have been noted in an invertebrate, the cephalochordate ''Branchiostoma' ...
s to
hemidesmosome
Hemidesmosomes are very small stud-like structures found in keratinocytes of the epidermis of skin that attach to the extracellular matrix. They are similar in form to desmosomes when visualized by electron microscopy; however, desmosomes attach ...
s. Consistent with the expression, mice defective for this gene show skin blistering and neurodegeneration.
Interactions
Dystonin has been shown to
interact with
collagen, type XVII, alpha 1,
,
and
erbin.
Loss of function in neurological disease
Several ''Dst'' mutant mouse lines have been described which share the common feature of having sensory neuron degeneration.
In humans, loss of dystonin function can cause
hereditary sensory and autonomic neuropathy type VI
and axonal
Charcot-Marie-Tooth disease.
In both human diseases, pathology is likely attributable to the loss of the dystonin-a2 protein isoform, which plays a role in neuronal autophagy.
See also
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Bullous pemphigoid
References
Further reading
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{{Cytoskeletal Proteins
EF-hand-containing proteins
Plakins