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

The MAP kinase phosphatase MKP-1 regulates BDNF-induced axon branching
The MAP kinase phosphatase MKP-1 regulates BDNF-induced axon branching
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.
1097-6256
1373-1379
Jeanneteau, Freddy
7da61a32-2f42-425d-a988-a7395e01a4cb
Deinhardt, Katrin
5f4fe23b-2317-499f-ba6d-e639a4885dc1
Miyoshi, Goichi
0b9eeffd-2847-471f-a4d6-571d1648fde4
Bennett, Anton M
749c1ca6-2bc0-416a-a117-b48977d1205f
Chao, Moses V
3ccc0c8d-3f7a-4d67-87a1-2a90636d1cd0
Jeanneteau, Freddy
7da61a32-2f42-425d-a988-a7395e01a4cb
Deinhardt, Katrin
5f4fe23b-2317-499f-ba6d-e639a4885dc1
Miyoshi, Goichi
0b9eeffd-2847-471f-a4d6-571d1648fde4
Bennett, Anton M
749c1ca6-2bc0-416a-a117-b48977d1205f
Chao, Moses V
3ccc0c8d-3f7a-4d67-87a1-2a90636d1cd0

Jeanneteau, Freddy, Deinhardt, Katrin, Miyoshi, Goichi, Bennett, Anton M and Chao, Moses V (2010) The MAP kinase phosphatase MKP-1 regulates BDNF-induced axon branching. Nature Neuroscience, 13 (11), 1373-1379. (doi:10.1038/nn.2655).

Record type: Article

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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Published date: 2010
Organisations: Faculty of Natural and Environmental Sciences, Centre for Biological Sciences

Identifiers

Local EPrints ID: 345197
URI: http://eprints.soton.ac.uk/id/eprint/345197
ISSN: 1097-6256
PURE UUID: 770c6e7c-53a3-4b19-8f81-4cc9e0118382
ORCID for Katrin Deinhardt: ORCID iD orcid.org/0000-0002-6473-5298

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Date deposited: 13 Nov 2012 11:09
Last modified: 26 Nov 2019 01:36

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