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Nat Neurosci. 2010 Nov;13(11):1373-9. doi: 10.1038/nn.2655. Epub 2010 Oct 10.

The MAP kinase phosphatase MKP-1 regulates BDNF-induced axon branching.

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Molecular Neurobiology Program, Skirball Institute of Biomolecular Medicine, New York, New York, USA.


The refinement of neural circuits during development depends on a dynamic process of branching of axons and dendrites that leads to synapse formation and connectivity. The neurotrophin brain-derived neurotrophic factor (BDNF) is essential for the outgrowth and activity-dependent remodeling of axonal arbors in vivo. However, the mechanisms that translate extracellular signals into the formation of axonal branches are incompletely understood. We found that MAP kinase phosphatase-1 (MKP-1) controls axon branching. MKP-1 expression induced by BDNF signaling caused spatiotemporal deactivation of c-jun N-terminal kinase (JNK), which reduced the phosphorylation of JNK substrates that destabilize microtubules. Indeed, neurons from mkp-1 null mice could not produce axon branches in response to BDNF. Our results identify a signaling mechanism that regulates axonal branching and provide a framework for studying the molecular mechanisms of innervation and axonal remodeling under normal and pathological conditions.

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