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

نویسندگان

  • 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
چکیده

Ca(2+) 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 Ca(2+)/calmodulin-dependent protein kinase CLICK-III (CL3)/CaMKIgamma, 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 Ca(2+)-dependent and lipid-raft-delineated switch that turns on extrinsic activity-regulated dendrite formation in developing cortical neurons.

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

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عنوان ژورنال:
  • Neuron

دوره 54  شماره 

صفحات  -

تاریخ انتشار 2007