CaMKIIβ-mediated LIM-kinase activation plays a crucial role in BDNF-induced neuritogenesis

Akihiko Saito, Ken Miyajima, Junichi Akatsuka, Hiroshi Kondo, Toshiya Mashiko, Tai Kiuchi, Kazumasa Ohashi, Kensaku Mizuno

    Research output: Contribution to journalArticlepeer-review

    24 Citations (Scopus)

    Abstract

    LIM-kinase 1 (LIMK1) regulates actin cytoskeletal reorganization by phosphorylating and inactivating actin-depolymerizing factor and cofilin. We examined the role of LIMK1 in brain-derived neurotrophic factor (BDNF)-induced neuritogenesis in primary-cultured rat cortical neurons. Knockdown of LIMK1 or expression of a kinase-dead LIMK1 mutant suppressed BDNF-induced enhancement of primary neurite formation. By contrast, expression of an active form of LIMK1 promoted primary neuritogenesis in the absence of BDNF. BDNF-induced neuritogenesis was inhibited by KN-93, an inhibitor of Ca2+/calmodulin-dependent protein kinases (CaMKs), but not by STO-609, an inhibitor of CaMK-kinase (CaMKK). CaMKK activity is required for the activation of CaMKI and CaMKIV, but not CaMKII, which suggests that CaMKII is principally involved in BDNF-induced enhancement of neuritogenesis. Knockdown of CaMKIIβ, but not CaMKIIα, suppressed BDNF-induced neuritogenesis. Active CaMKIIβ promoted neuritogenesis, and this promotion was inhibited by knockdown of LIMK1, indicating that CaMKIIβ is involved in BDNF-induced neuritogenesis via activation of LIMK1. Furthermore, in vitro kinase assays revealed that CaMKIIβ phosphorylates LIMK1 at Thr-508 in the kinase domain and activates the cofilin-phosphorylating activity of LIMK1. In summary, these results suggest that CaMKIIβ-mediated activation of LIMK1 plays a crucial role in BDNF-induced enhancement of primary neurite formation.

    Original languageEnglish
    Pages (from-to)533-543
    Number of pages11
    JournalGenes to Cells
    Volume18
    Issue number7
    DOIs
    Publication statusPublished - 2013 Jul

    ASJC Scopus subject areas

    • Genetics
    • Cell Biology

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