title: JNK1 is required for maintenance of neuronal microtubules and controls phosphorylation of microtubule-associated proteins.
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.
authors.affiliation: Laboratory of Gene Regulation and Signal Transduction, University of California, San Diego, School of Medicine, La Jolla, CA 92037, USA.
authors.forename: Lufen
authors.initials: L
authors.lastname: Chang
authors.forename: Ying
authors.initials: Y
authors.lastname: Jones
authors.forename: Mark H
authors.initials: MH
authors.lastname: Ellisman
authors.forename: Lawrence S B
authors.initials: LS
authors.lastname: Goldstein
authors.forename: Michael
authors.initials: M
authors.lastname: Karin
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D002454:Cell Differentiation / Q000235:genetics*; D002490:Central Nervous System / Q000201:enzymology* / Q000254:growth & development* / Q000648:ultrastructure; D003712:Dendrites / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D051379:Mice; D018345:Mice, Knockout; D008854:Microscopy, Electron; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D008870:Microtubules / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D048055:Mitogen-Activated Protein Kinase 8; D020928:Mitogen-Activated Protein Kinases / Q000172:deficiency* / Q000235:genetics; D009410:Nerve Degeneration / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D009474:Neurons / Q000201:enzymology* / Q000648:ultrastructure; D010766:Phosphorylation; D011485:Protein Binding / Q000235:genetics
chemical_list: D008869:Microtubule-Associated Proteins; D048055:Mitogen-Activated Protein Kinase 8; D020928:Mitogen-Activated Protein Kinases