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
Collagen XVII, previously called BP180, is a transmembrane protein which plays a critical role in maintaining the linkage between the intracellular and the extracellular structural elements involved in epidermal adhesion, identified by Diaz and c ...
,
DCTN1
Dynactin subunit 1 is a protein that in humans is encoded by the ''DCTN1'' gene.
Function
This gene encodes the largest subunit of dynactin, a macromolecular complex consisting of 23 subunits (11 individual proteins ranging in size from 22 ...
,
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
Hereditary sensory and autonomic neuropathy (HSAN) or hereditary sensory neuropathy (HSN) is a condition used to describe any of the types of this disease which inhibit sensation.
They are less common than Charcot-Marie-Tooth disease.
Classif ...
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
Bullous pemphigoid (a type of pemphigoid) is an autoimmune pruritic skin disease that typically occurs in people aged over 60, that may involve the formation of blisters ( bullae) in the space between the epidermal and dermal skin layers. It is ...
References
Further reading
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{{Cytoskeletal Proteins
EF-hand-containing proteins
Plakins