Abstract
Sensory neurodegeneration occurs in mice defective in BPAG1, a gene encoding cytoskeletal linker proteins capable of anchoring neuronal intermediate filaments to actin cytoskeleton. While BPAG1 null mice fail to anchor neurofilaments (NFs), BPAG1/NF null mice still degenerate in the absence of NFs. We report a novel neural splice form that lacks the actin-binding domain and instead binds and stabilizes microtubules. This interaction is functionally important; in mice and in vitro, neurons lacking BPAG1 display short, disorganized, and unstable microtubules defective in axonal transport. Ironically, BPAG1 neural isoforms represent microtubule-associated proteins that when absent lead to devastating consequences. Moreover, BPAG1 can functionally account for the extraordinary stability of axonal microtubules necessary for transport over long distances. Its isoforms interconnect all three cytoskeletal networks, a feature apparently central to neuronal survival.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Actin Cytoskeleton / metabolism
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Actin Cytoskeleton / ultrastructure
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Animals
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Axonal Transport / physiology
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Axons / chemistry
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Axons / metabolism
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Axons / ultrastructure
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Carrier Proteins*
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Cells, Cultured
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Cytoskeletal Proteins / chemistry
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Cytoskeletal Proteins / genetics*
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Cytoskeletal Proteins / metabolism*
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Desmoplakins
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Dystonin
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Mice
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Mice, Knockout
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Microfilament Proteins / metabolism
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Microscopy, Immunoelectron
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Microtubules / metabolism*
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Microtubules / ultrastructure
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Molecular Sequence Data
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Nerve Tissue Proteins / chemistry
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Nerve Tissue Proteins / genetics*
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Nerve Tissue Proteins / metabolism*
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Neurofilament Proteins / metabolism
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Neurons, Afferent / cytology
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Neurons, Afferent / metabolism
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Neurons, Afferent / ultrastructure
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Protein Structure, Tertiary
Substances
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Carrier Proteins
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Cytoskeletal Proteins
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Desmoplakins
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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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neurofilament protein L