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Light-mediated Reversible Modulation of the Mitogen-activated Protein Kinase Pathway during Cell Differentiation and Xenopus Embryonic Development
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Published on: June 15, 2017

DCX, a new mediator of the JNK pathway

Amos Gdalyahu1, Indraneel Ghosh, Talia Levy

  • 1Department of Molecular Genetics, The Weizmann Institute of Science, Rehovot, Israel.

The EMBO Journal
|February 7, 2004
PubMed

Insights

Doublecortin (DCX) is crucial for neuronal migration. This study reveals DCX interacts with JNK signaling, impacting neurite outgrowth and neuron movement during brain development.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Genetics

Background:

  • Mutations in the X-linked gene Doublecortin (DCX) cause lissencephaly in males and neuronal migration defects in females.
  • The precise molecular mechanisms and signaling pathways involving DCX in neuronal migration remain incompletely understood.

Purpose of the Study:

  • To elucidate the role of Doublecortin (DCX) in neuronal migration signaling pathways.
  • To investigate the interaction of DCX with c-Jun N-terminal kinase (JNK) and its substrates.

Main Methods:

  • Demonstrated DCX as a substrate of JNK.
  • Investigated the interaction between DCX, JNK, and JNK interacting protein (JIP).
  • Analyzed the effects of JNK phosphorylation site mutations in DCX on neuronal migration and neurite outgrowth.

Main Results:

  • Established that DCX interacts with JNK and JIP, forming a signaling module in developing brain neurons.
  • Showed DCX localization at neurite tips is dependent on JIP and kinesin interactions.
  • Phosphorylation of DCX by JNK in growth cones is critical; mutated DCX impaired neurite outgrowth and neuronal migration velocity.

Conclusions:

  • DCX is a key component of a JNK-mediated signaling pathway regulating neuronal migration.
  • The interaction of DCX with molecular motor regulators like kinesin, influenced by JNK phosphorylation, is vital for directional neuronal movement.

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