PMID:16000625

Citation	Björkblom, B, Ostman, N, Hongisto, V, Komarovski, V, Filén, JJ, Nyman, TA, Kallunki, T, Courtney, MJ and Coffey, ET (2005) Constitutively active cytoplasmic c-Jun N-terminal kinase 1 is a dominant regulator of dendritic architecture: role of microtubule-associated protein 2 as an effector. J. Neurosci. 25:6350-61
Abstract	Normal functioning of the nervous system requires precise regulation of dendritic shape and synaptic connectivity. Here, we report a severe impairment of dendritic structures in the cerebellum and motor cortex of c-Jun N-terminal kinase 1 (JNK1)-deficient mice. Using an unbiased screen for candidate mediators, we identify the dendrite-specific high-molecular-weight microtubule-associated protein 2 (MAP2) as a JNK substrate in the brain. We subsequently show that MAP2 is phosphorylated by JNK in intact cells and that MAP2 proline-rich domain phosphorylation is decreased in JNK1-/- brain. We developed compartment-targeted JNK inhibitors to define whether a functional relationship exists between the physiologically active, cytosolic pool of JNK and dendritic architecture. Using these, we demonstrate that cytosolic, but not nuclear, JNK determines dendritic length and arbor complexity in cultured neurons. Moreover, we confirm that MAP2-dependent process elongation is enhanced after activation of JNK. Using JNK1-/- neurons, we reveal a dominant role for JNK1 over ERK in regulating dendritic arborization, whereas ERK only regulates dendrite shape under conditions in which JNK activity is low (JNK1-/- neurons). These results reveal a novel antagonism between JNK and ERK, potentially providing a mechanism for fine-tuning the dendritic arbor. Together, these data suggest that JNK phosphorylation of MAP2 plays an important role in defining dendritic architecture in the brain.
Links	PubMed Online version:10.1523/JNEUROSCI.1517-05.2005
Keywords	Animals; COS Cells; Cell Differentiation; Cell Nucleus/enzymology; Cells, Cultured/enzymology; Cells, Cultured/ultrastructure; Cercopithecus aethiops; Cerebellar Cortex/cytology; Cerebellar Cortex/enzymology; Cerebellar Cortex/growth & development; Cytosol/enzymology; Dendrites/ultrastructure; Mice; Mice, Knockout; Microtubule-Associated Proteins/physiology; Mitogen-Activated Protein Kinase 1/metabolism; Mitogen-Activated Protein Kinase 3/metabolism; Mitogen-Activated Protein Kinase 8/antagonists & inhibitors; Mitogen-Activated Protein Kinase 8/deficiency; Mitogen-Activated Protein Kinase 8/genetics; Mitogen-Activated Protein Kinase 8/physiology; Motor Cortex/cytology; Motor Cortex/enzymology; Neurons/ultrastructure; Phosphorylation; Prosencephalon/cytology; Prosencephalon/enzymology; Protein Processing, Post-Translational; Rats; Rats, Sprague-Dawley; Recombinant Fusion Proteins/physiology; Transfection
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
MOUSE:MK08		GO:0048813: dendrite morphogenesis	ECO:0000315:		P		Figure 4 shows that inhibition of JNK1 results in shorter and more numerous dendritic processes. Figures 7 and 8 support JNK1 involvement in the development of the shape and size of the dendritic processes by pictures and analyzation of the dendrites.	complete CACAO 4643
MOUSE:MK08	involved_in	GO:0048813: dendrite morphogenesis	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete

References

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