Role of dual leucine zipper-bearing kinase (DLK/MUK/ZPK) in axonal growth

Kaoru Eto, Takeshi Kawauchi, Makiko Osawa, Hidenori Tabata, Kazunori Nakajima

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

In developing cerebral cortices, post-mitotic neurons migrate toward the pial surface, elongating their axons concurrently. It has been reported that targeted-deletion of the dual leucine zipper-bearing kinase (DLK)/mitogen-activated protein kinase upstream protein kinase (MUK)/leucine-zipper protein kinase (ZPK) gene, which encodes a MAP kinase kinase kinase (MAPKKK) for c-Jun N-terminal kinase (JNK), leads to a neuronal migration-defect and hypoplasia of axonal fiber tracts including those of the anterior commissure and corpus callosum. However, there is no evidence that DLK directly regulates axonal development, because another possibility, i.e. that the defective axonal development in the DLK mutant might be caused secondary to migration failure cannot be ruled out. In this study, we first examined the distributions of DLK mRNA and its protein in the developing cerebral cortex, and found that major portion of DLK proteins appear to be transported into axons. Using dissociated cortical neurons and PC12 cells, we provide direct evidence that DLK regulates axonal elongation. Furthermore, knock-down of DLK decreased the phosphorylation of JNK and its substrate, microtubule-associated protein 1B (MAP1B), which is known to be involved in axonal elongation. These results suggest that the DLK/MUK/ZPK-JNK pathway directly regulates axonal growth through phosphorylation of MAP1B.

Original languageEnglish
Pages (from-to)37-45
Number of pages9
JournalNeuroscience Research
Volume66
Issue number1
DOIs
Publication statusPublished - 2010 Jan

Fingerprint

JNK Mitogen-Activated Protein Kinases
Growth
Cerebral Cortex
Axons
Phosphorylation
MAP Kinase Kinase Kinases
Neurons
Corpus Callosum
PC12 Cells
Mitogen-Activated Protein Kinases
Proteins
Messenger RNA
mitogen-activated protein kinase kinase kinase 12
Genes
microtubule-associated protein 1B

Keywords

  • Axonal growth
  • Cerebral cortex
  • Development
  • DLK
  • JNK
  • MAP1B

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Role of dual leucine zipper-bearing kinase (DLK/MUK/ZPK) in axonal growth. / Eto, Kaoru; Kawauchi, Takeshi; Osawa, Makiko; Tabata, Hidenori; Nakajima, Kazunori.

In: Neuroscience Research, Vol. 66, No. 1, 01.2010, p. 37-45.

Research output: Contribution to journalArticle

Eto, Kaoru ; Kawauchi, Takeshi ; Osawa, Makiko ; Tabata, Hidenori ; Nakajima, Kazunori. / Role of dual leucine zipper-bearing kinase (DLK/MUK/ZPK) in axonal growth. In: Neuroscience Research. 2010 ; Vol. 66, No. 1. pp. 37-45.
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