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

Authors
Journal
Nature Neuroscience
1097-6256
Publisher
Nature Publishing Group
Publication Date
Volume
13
Issue
11
Identifiers
DOI: 10.1038/nn.2655
Keywords
  • Article
Disciplines
  • Biology
  • Medicine

Abstract

The refinement of neural circuits during development depends upon a dynamic process of branching of axons and dendrites that leads to synapse formation and connectivity. The neurotrophin BDNF plays an essential role in the outgrowth and activity-dependent remodeling of axonal arbors in vivo. However, the mechanisms that translate extracellular signals into axonal branch formation are incompletely understood. Here we report that the MAP kinase phosphatase-1 (MKP-1) controls axon branching. MKP-1 expression induced by BDNF signaling exerts spatio-temporal deactivation of JNK, which negatively regulates the phosphorylation of JNK substrates that impinge upon microtubule destabilization. Indeed, neurons from mkp-1 null mice were unable to produce axon branches in response to BDNF. Our results indicate a heretofore-unknown signaling mechanism to regulate axonal branching and provide a framework for studying the molecular mechanism of innervation and axonal remodeling under normal and pathological conditions.

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