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Chang, L, Jones, Y, Ellisman, MH, Goldstein, LS and Karin, M (2003) JNK1 is required for maintenance of neuronal microtubules and controls phosphorylation of microtubule-associated proteins. Dev. Cell 4:521-33


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.




Animals; Axons/metabolism; Axons/pathology; Axons/ultrastructure; Cell Differentiation/genetics; Central Nervous System/enzymology; Central Nervous System/growth & development; Central Nervous System/ultrastructure; Dendrites/metabolism; Dendrites/pathology; Dendrites/ultrastructure; Mice; Mice, Knockout; Microscopy, Electron; Microtubule-Associated Proteins/genetics; Microtubule-Associated Proteins/metabolism; Microtubules/genetics; Microtubules/metabolism; Microtubules/ultrastructure; Mitogen-Activated Protein Kinase 8; Mitogen-Activated Protein Kinases/deficiency; Mitogen-Activated Protein Kinases/genetics; Nerve Degeneration/enzymology; Nerve Degeneration/genetics; Nerve Degeneration/pathology; Neurons/enzymology; Neurons/ultrastructure; Phosphorylation; Protein Binding/genetics



Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status


GO:0004708: MAP kinase kinase activity



Figure 5B shows that JNK1 efficiently phosphorylates MAP and 5D shows that it is specific. At low concentrations, JNK1 is a predominant MAP2 kinase. In Figure 6A, JNK1 deficient mice displayed 3 fold lower labelling of MAP2 and in 6B MAP2 polypeptides are significantly lowered in JNK1 deficient mice. JNK1 is an important MAP2 kinase.

CACAO 4653

See also


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