Abstract
Typified by rapid degeneration of sensory neurons, dystonia musculorum mice have a defective BPAG1 gene, known to be expressed in epidermis. We report a neuronal splice form, BPAG1n, which localizes to sensory axons. Both isoforms have a coiled-coil rod, followed by a carboxy domain that associates with intermediate filaments. However, the amino terminus of BPAG1n differs from BPAG1e in that it contains a functional actin-binding domain. In transfected cells, BPAG1n coaligns neurofilaments and microfilaments, establishing this as a cytoskeletal protein interconnecting actin and intermediate filament cytoskeletons. In BPAG1 null mice, axonal architecture is markedly perturbed, consistent with a failure to tether neurofilaments to the actin cytoskeleton and underscoring the physiological relevance of this protein.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Actin Cytoskeleton / chemistry*
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Alternative Splicing
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Animals
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Autoantigens / physiology*
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Brain Chemistry
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Carrier Proteins*
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Collagen Type XVII
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Collagen*
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Cytoskeletal Proteins*
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Dystonin
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Fluorescent Antibody Technique
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Ganglia, Spinal / ultrastructure
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Gene Expression
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Humans
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In Situ Hybridization
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Intermediate Filaments / chemistry*
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Mice
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Mice, Mutant Strains
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Microfilament Proteins / physiology*
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Molecular Weight
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Nerve Tissue Proteins / chemistry*
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Neurofilament Proteins / metabolism*
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Neurons, Afferent / ultrastructure*
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Non-Fibrillar Collagens*
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Protein Binding
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RNA, Messenger / genetics
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Spinal Cord / chemistry
Substances
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Autoantigens
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Carrier Proteins
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Cytoskeletal Proteins
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DST protein, human
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Dst protein, mouse
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Dystonin
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Microfilament Proteins
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Nerve Tissue Proteins
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Neurofilament Proteins
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Non-Fibrillar Collagens
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RNA, Messenger
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Collagen