Regulation of Dendritogenesis via a Lipid-Raft-Associated Ca2+/Calmodulin-Dependent Protein Kinase CLICK-III/CaMKIγ

Sayaka Takemoto-Kimura, Natsumi Ageta-Ishihara, Mio Nonaka, Aki Adachi-Morishima, Tatsuo Mano, Michiko Okamura, Hajime Fujii, Toshimitsu Fuse, Mikio Hoshino, Shingo Suzuki, Masami Kojima, Masayoshi Mishina, Hiroyuki Okuno, Haruhiko Bito

Research output: Contribution to journalArticlepeer-review

90 Citations (Scopus)

Abstract

Ca2+ signaling plays a central role in activity-dependent regulation of dendritic arborization, but key molecular mechanisms downstream of calcium elevation remain poorly understood. Here we show that the C-terminal region of the Ca2+/calmodulin-dependent protein kinase CLICK-III (CL3)/CaMKIγ, a membrane-anchored CaMK, was uniquely modified by two sequential lipidification steps: prenylation followed by a kinase-activity-regulated palmitoylation. These modifications were essential for CL3 membrane anchoring and targeting into detergent-resistant lipid microdomains (or rafts) in the dendrites. We found that CL3 critically contributed to BDNF-stimulated dendritic growth. Raft insertion of CL3 specifically promoted dendritogenesis of cortical neurons by acting upstream of RacGEF STEF and Rac, both present in lipid rafts. Thus, CL3 may represent a key element in the Ca2+-dependent and lipid-raft-delineated switch that turns on extrinsic activity-regulated dendrite formation in developing cortical neurons.

Original languageEnglish
Pages (from-to)755-770
Number of pages16
JournalNeuron
Volume54
Issue number5
DOIs
Publication statusPublished - 2007 Jun 7

Keywords

  • CELLBIO
  • DEVBIO
  • MOLNEURO

ASJC Scopus subject areas

  • Neuroscience(all)

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