A CaMKII beta signaling pathway at the centrosome regulates dendrite patterning in the brain

作者：Puram Sidharth V; Kim Albert H; Ikeuchi Yoshiho; Wilson Grady Joshua T; Merdes Andreas; Gygi Steven P; Bonni Azad^*

来源：Nature Neuroscience, 2011, 14(8): 973-U58.

DOI：10.1038/nn.2857

The protein kinase calcium/calmodulin-dependent kinase II (CaMKII) predominantly consists of the alpha and beta isoforms in the brain. Although CaMKII alpha functions have been elucidated, the isoform-specific catalytic functions of CaMKII beta have remained unknown. Using knockdown analyses in primary rat neurons and in the rat cerebellar cortex in vivo, we report that CaMKII beta operates at the centrosome in a CaMKII alpha-independent manner to drive dendrite retraction and pruning. We also find that the targeting protein PCM1 (pericentriolar material 1) localizes CaMKII beta to the centrosome. Finally, we uncover the E3 ubiquitin ligase Cdc20-APC (cell division cycle 20-anaphase promoting complex) as a centrosomal substrate of CaMKII beta. CaMKII beta 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 CaMKII beta that regulates ubiquitin signaling at the centrosome and thereby orchestrates dendrite patterning, with important implications for neuronal connectivity in the brain.

• 出版日期2011-8