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

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

doi:10.1016/j.neuron.2007.05.021

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

Neuron. 2007 Jun 7;54(5):755-70. doi: 10.1016/j.neuron.2007.05.021.

Authors

Sayaka Takemoto-Kimura¹, 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

Affiliation

¹ Department of Neurochemistry, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan.

PMID: 17553424
DOI: 10.1016/j.neuron.2007.05.021

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Brain-Derived Neurotrophic Factor / metabolism
Brain-Derived Neurotrophic Factor / pharmacology
COS Cells
Calcium Signaling / physiology*
Calcium-Calmodulin-Dependent Protein Kinase Type 1
Calcium-Calmodulin-Dependent Protein Kinases / chemistry
Calcium-Calmodulin-Dependent Protein Kinases / metabolism*
Cell Differentiation / physiology*
Cerebral Cortex / cytology
Cerebral Cortex / embryology*
Cerebral Cortex / metabolism
Chlorocebus aethiops
Dendrites / metabolism*
Dendrites / ultrastructure
Glycosylphosphatidylinositols / metabolism
Membrane Microdomains / metabolism*
Mice
Palmitic Acid / metabolism
Protein Prenylation / physiology
Protein Processing, Post-Translational / physiology
Protein Structure, Tertiary / physiology
Rats
Rats, Sprague-Dawley
rac GTP-Binding Proteins / metabolism

Substances

Brain-Derived Neurotrophic Factor
Glycosylphosphatidylinositols
Palmitic Acid
Calcium-Calmodulin-Dependent Protein Kinase Type 1
Calcium-Calmodulin-Dependent Protein Kinases
Camk1 protein, mouse
Camk1 protein, rat
Camk1g protein, mouse
Pnck protein, mouse
Pnck protein, rat
rac GTP-Binding Proteins