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

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 spatiotemporal
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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Identifiers

ORCID for Katrin Deinhardt: orcid.org/0000-0002-6473-5298

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