PMID: 21725312

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