Abstract
Microtubules (MTs) play an important role in elaboration and maintenance of axonal and dendritic processes. MT dynamics are modulated by MT-associated proteins (MAPs), whose activities are regulated by protein phosphorylation. We found that a member of the c-Jun NH(2)-terminal protein kinase (JNK) subgroup of MAP kinases, JNK1, is involved in regulation of MT dynamics in neuronal cells. Jnk1(-/-) mice exhibit disrupted anterior commissure tract formation and a progressive loss of MTs within axons and dendrites. MAP2 and MAP1B polypeptides are hypophosphorylated in Jnk1(-/-) brains, resulting in compromised ability to bind MTs and promote their assembly. These results suggest that JNK1 is required for maintaining the cytoskeletal integrity of neuronal cells and is a critical regulator of MAP activity and MT assembly.
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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Animals
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Axons / metabolism
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Axons / pathology
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Axons / ultrastructure
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Cell Differentiation / genetics*
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Central Nervous System / enzymology*
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Central Nervous System / growth & development*
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Central Nervous System / ultrastructure
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Dendrites / metabolism
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Dendrites / pathology
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Dendrites / ultrastructure
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Mice
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Mice, Knockout
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Microscopy, Electron
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Microtubule-Associated Proteins / genetics
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Microtubule-Associated Proteins / metabolism*
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Microtubules / genetics
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Microtubules / metabolism*
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Microtubules / ultrastructure
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Mitogen-Activated Protein Kinase 8
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Mitogen-Activated Protein Kinases / deficiency*
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Mitogen-Activated Protein Kinases / genetics
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Nerve Degeneration / enzymology
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Nerve Degeneration / genetics
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Nerve Degeneration / pathology
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Neurons / enzymology*
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Neurons / ultrastructure
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Phosphorylation
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Protein Binding / genetics
Substances
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Microtubule-Associated Proteins
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Mitogen-Activated Protein Kinase 8
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Mitogen-Activated Protein Kinases