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Regulation of dendritogenesis via a lipid-raft-associated Ca2+/calmodulin-dependent protein kinase CLICK-III/CaMKIgamma.

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.

Pubmed ID: 17553424


  • Takemoto-Kimura S
  • Ageta-Ishihara N
  • Nonaka M
  • Adachi-Morishima A
  • Mano T
  • Okamura M
  • Fujii H
  • Fuse T
  • Hoshino M
  • Suzuki S
  • Kojima M
  • Mishina M
  • Okuno H
  • Bito H



Publication Data

June 7, 2007

Associated Grants


Mesh Terms

  • Animals
  • Brain-Derived Neurotrophic Factor
  • COS Cells
  • Calcium Signaling
  • Calcium-Calmodulin-Dependent Protein Kinase Type 1
  • Calcium-Calmodulin-Dependent Protein Kinases
  • Cell Differentiation
  • Cercopithecus aethiops
  • Cerebral Cortex
  • Dendrites
  • Glycosylphosphatidylinositols
  • Membrane Microdomains
  • Mice
  • Palmitic Acid
  • Protein Prenylation
  • Protein Processing, Post-Translational
  • Protein Structure, Tertiary
  • Rats
  • Rats, Sprague-Dawley
  • rac GTP-Binding Proteins