Liprinα1 degradation by calcium/calmodulin-dependent protein kinase II regulates LAR receptor tyrosine phosphatase distribution and dendrite development

Neural activity regulates dendrite and synapse development, but the underlying molecular mechanisms are unclear. Ca2+/calmodulin-dependent protein kinase 11 (CaMKII) is an important sensor of synaptic activity, and the scaffold protein liprin alpha 1 is involved in pre- and postsynaptic maturation. Here we show that synaptic activity can suppress liprin alpha 1 protein level by two pathways: CaMKII-mediated degradation and the ubiquitin-proteasome system. In hippocampal neurons, liprin alpha 1 mutants that are immune to CaMKII degradation impair dendrite arborization, reduce spine and synapse number, and inhibit dendritic targeting of receptor tyrosine phosphatase LAR, which is important for dendrite development. Thus, regulated degradation of liprin alpha 1 is important for proper LAR receptor distribution, and could provide a mechanism for localized control of dendrite and synapse morphogenesis by activity and CaMKII.