title: A CaMKIIβ signaling pathway at the centrosome regulates dendrite patterning in the brain.
abstract: The protein kinase calcium/calmodulin-dependent kinase II (CaMKII) predominantly consists of the α and β isoforms in the brain. Although CaMKIIα functions have been elucidated, the isoform-specific catalytic functions of CaMKIIβ have remained unknown. Using knockdown analyses in primary rat neurons and in the rat cerebellar cortex in vivo, we report that CaMKIIβ operates at the centrosome in a CaMKIIα-independent manner to drive dendrite retraction and pruning. We also find that the targeting protein PCM1 (pericentriolar material 1) localizes CaMKIIβ to the centrosome. Finally, we uncover the E3 ubiquitin ligase Cdc20-APC (cell division cycle 20-anaphase promoting complex) as a centrosomal substrate of CaMKIIβ. CaMKIIβ phosphorylates Cdc20 at Ser51, which induces Cdc20 dispersion from the centrosome, thereby inhibiting centrosomal Cdc20-APC activity and triggering the transition from growth to retraction of dendrites. Our findings define a new, isoform-specific function for CaMKIIβ that regulates ubiquitin signaling at the centrosome and thereby orchestrates dendrite patterning, with important implications for neuronal connectivity in the brain.
authors: Department of Pathology, Harvard Medical School, Boston, Massachusetts, USA.
authors: Sidharth V
authors: SV
authors: Puram
authors: Albert H
authors: AH
authors: Kim
authors: Yoshiho
authors: Y
authors: Ikeuchi
authors: Joshua T
authors: JT
authors: Wilson-Grady
authors: Andreas
authors: A
authors: Merdes
authors: Steven P
authors: SP
authors: Gygi
authors: Azad
authors: A
authors: Bonni
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D054737:Calcium-Calmodulin-Dependent Protein Kinase Kinase / Q000235:genetics / Q000378:metabolism*; D064199:Cdc20 Proteins; D018797:Cell Cycle Proteins / Q000378:metabolism; D002478:Cells, Cultured; D018385:Centrosome / Q000502:physiology* / Q000648:ultrastructure; D002531:Cerebellum / Q000166:cytology*; D002522:Chlorocebus aethiops; D003598:Cytoskeletal Proteins / Q000378:metabolism; D003712:Dendrites / Q000235:genetics / Q000502:physiology* / Q000648:ultrastructure; D018274:Electroporation / Q000379:methods; D018507:Gene Expression Regulation, Developmental; D049452:Green Fluorescent Proteins / Q000235:genetics; D047468:Immunoprecipitation; D013058:Mass Spectrometry; D018613:Microscopy, Confocal; D046529:Microscopy, Electron, Transmission / Q000379:methods; D009474:Neurons / Q000166:cytology* / Q000502:physiology; D009924:Organ Culture Techniques; D034622:RNA Interference / Q000502:physiology; D051381:Rats; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*; D018709:Statistics, Nonparametric; D014162:Transfection; D025801:Ubiquitin / Q000378:metabolism
chemical_list: D064199:Cdc20 Proteins; C577491:Cdc20 protein, mouse; D018797:Cell Cycle Proteins; D003598:Cytoskeletal Proteins; C490114:Pcm1 protein, mouse; D025801:Ubiquitin; D049452:Green Fluorescent Proteins; D054737:Calcium-Calmodulin-Dependent Protein Kinase Kinase