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.
Takemoto-Kimura
Sayaka
S
Department of Neurochemistry, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan.
Ageta-Ishihara
Natsumi
N
Nonaka
Mio
M
Adachi-Morishima
Aki
A
Mano
Tatsuo
T
Okamura
Michiko
M
Fujii
Hajime
H
Fuse
Toshimitsu
T
Hoshino
Mikio
M
Suzuki
Shingo
S
Kojima
Masami
M
Mishina
Masayoshi
M
Okuno
Hiroyuki
H
Bito
Haruhiko
H
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism / Q000494:pharmacology; D019556:COS Cells; D020013:Calcium Signaling / Q000502:physiology*; D054729:Calcium-Calmodulin-Dependent Protein Kinase Type 1; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000737:chemistry / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology*; D002540:Cerebral Cortex / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D002522:Chlorocebus aethiops; D003712:Dendrites / Q000378:metabolism* / Q000648:ultrastructure; D017261:Glycosylphosphatidylinositols / Q000378:metabolism; D021962:Membrane Microdomains / Q000378:metabolism*; D051379:Mice; D019308:Palmitic Acid / Q000378:metabolism; D017368:Protein Prenylation / Q000502:physiology; D011499:Protein Processing, Post-Translational / Q000502:physiology; D017434:Protein Structure, Tertiary / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020744:rac GTP-Binding Proteins / Q000378:metabolism
D019208:Brain-Derived Neurotrophic Factor; D017261:Glycosylphosphatidylinositols; D019308:Palmitic Acid; D054729:Calcium-Calmodulin-Dependent Protein Kinase Type 1; D017871:Calcium-Calmodulin-Dependent Protein Kinases; C517598:Camk1 protein, mouse; C517599:Camk1 protein, rat; C517605:Camk1g protein, mouse; C517681:Pnck protein, mouse; C517682:Pnck protein, rat; D020744:rac GTP-Binding Proteins