Abstract
The dystrophin glycoprotein complex (DGC) is a multimeric protein assembly associated with either the X-linked cytoskeletal protein dystrophin or its autosomal homologue utrophin. In striated muscle cells, the DGC links the extracellular matrix to the actin cytoskeleton and mediates three major functions: structural stability of the plasma membrane, ion homeostasis, and transmembrane signaling. Mutations affecting the DGC underlie major forms of congenital muscle dystrophies. The DGC is prominent also in the central and peripheral nervous system and in tissues with a secretory function or which form barriers between functional compartments, such as the blood-brain barrier, choroid plexus, or kidney. A considerable molecular heterogeneity arises from cell-specific expression of its constituent proteins, notably short C-terminal isoforms of dystrophin. Experimentally, the generation of mice carrying targeted gene deletions affecting the DGC has clarified the interdependence of DGC proteins for assembly of the complex and revealed its importance for brain development and regulation of the 'milieu intérieur. Here, we focus on recent studies of the DGC in brain, blood-brain barrier and choroid plexus, retina, and kidney and discuss the role of dystrophin isoforms and utrophin for assembly of the complex in these tissues.
Publication types
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Research Support, Non-U.S. Gov't
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Review
MeSH terms
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Actin Cytoskeleton / metabolism
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Animals
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Blood-Brain Barrier
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Brain Chemistry
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Carrier Proteins / metabolism
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Choroid Plexus / metabolism
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Dystroglycans / deficiency
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Dystroglycans / genetics
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Dystroglycans / physiology
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Dystrophin / chemistry
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Dystrophin / deficiency
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Dystrophin / genetics
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Dystrophin / physiology*
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Dystrophin-Associated Protein Complex / chemistry
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Dystrophin-Associated Protein Complex / physiology*
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Dystrophin-Associated Proteins / deficiency
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Dystrophin-Associated Proteins / genetics
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Dystrophin-Associated Proteins / metabolism
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Eye Proteins / genetics
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Eye Proteins / physiology
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Humans
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Kidney / metabolism
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Membrane Proteins / metabolism
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Mice
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Mice, Inbred mdx
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Mice, Knockout
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Models, Biological
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Muscle Proteins / deficiency
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Muscle Proteins / genetics
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Muscle Proteins / physiology
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Muscle, Skeletal / metabolism
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Muscular Dystrophy, Animal / genetics
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Muscular Dystrophy, Animal / metabolism
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Muscular Dystrophy, Duchenne / genetics
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Muscular Dystrophy, Duchenne / metabolism
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Neoplasm Proteins / metabolism
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Nerve Tissue Proteins / deficiency
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Nerve Tissue Proteins / genetics
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Nerve Tissue Proteins / physiology
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Neuromuscular Junction / chemistry
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Neuromuscular Junction / physiology
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Organ Specificity
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Protein Binding
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Protein Isoforms / physiology
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Retina / metabolism
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Sarcoglycans / metabolism
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Utrophin / deficiency
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Utrophin / genetics
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Utrophin / physiology*
Substances
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Carrier Proteins
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Dystrophin
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Dystrophin-Associated Protein Complex
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Dystrophin-Associated Proteins
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Eye Proteins
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Membrane Proteins
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Muscle Proteins
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Neoplasm Proteins
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Nerve Tissue Proteins
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Protein Isoforms
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SSPN protein, human
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Sarcoglycans
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Sspn protein, mouse
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Utrophin
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dystrobrevin
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syntrophin
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Dystroglycans