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
Department of Neurochemistry, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan.
Neuron 2007 Jun 7Ca(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.
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. Regulation of dendritogenesis via a lipid-raft-associated Ca2+/calmodulin-dependent protein kinase CLICK-III/CaMKIgamma. Neuron. 2007 Jun 7;54(5):755-70
PMID: 17553424
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