JNK1 is required for maintenance of neuronal microtubules and controls phosphorylation of microtubule-associated proteins.
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.
Chang
Lufen
L
Laboratory of Gene Regulation and Signal Transduction, University of California, San Diego, School of Medicine, La Jolla, CA 92037, USA.
Jones
Ying
Y
Ellisman
Mark H
MH
Goldstein
Lawrence S B
LS
Karin
Michael
M
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
D008869:Microtubule-Associated Proteins; D048055:Mitogen-Activated Protein Kinase 8; D020928:Mitogen-Activated Protein Kinases