Selective Regulation of Neurite Extension and Synapse Formation by the β but not the α Isoform of CaMKII

Selective Regulation of Neurite Extension and Synapse Formation by the ␤ but not the ␣ Isoform of CaMKII volves Ca 2ϩ /calmodulin (CaM) binding to each subunit as well as an autophosphorylation step that can render each subunit partially autonomous from Ca 2ϩ /CaM bind-NMDA receptor-triggered translocation to postsynaptic sites (Shen and Meyer, 1999; Shen et al., 2000), presumably as a result of a binding to the NMDA receptor itself (Bayer et al., 2001). CaMKII has been studied extensively Summary in hippocampal and other neurons as a mediator of plasticity and memory (Silva et al. ronal plasticity mechanisms that can lead to the addi-2002; Fink and Meyer, 2002). In a well-supported model tion of synaptic contacts in developing neurons and for enhancement of synaptic strength, Ca 2ϩ entering changes in the number of synapses in mature neurons. through NMDA receptor activates CaMKII␣, which in Here we show that Ca 2؉ /calmodulin-dependent pro-turn leads to an increase in the number (Shi et al., 1999, tein kinase II (CaMKII) regulates movement, extension, 2001) as well as the conductivity of AMPA receptors and branching of filopodia and fine dendrites as well within the postsynaptic membrane (Derkach et al., 1999). as the number of synapses in hippocampal neurons. We focused our study on whether CaMKII may not Only CaMKII␤, which peaks in expression early in de-only regulate the strength of synapses but also be in-velopment, but not CaMKII␣, has this morphogenic volved in regulating the morphology of dendrites. This activity. A small insert in CaMKII␤, which is absent in hypothesis was in part motivated by our previous study CaMKII␣, confers regulated F-actin localization to the where we showed that the second most prominent enzyme and enables selective upregulation of den-CaMKII isoform, CaMKII␤, is localized to the actin cy-dritic motility. These results show that the two main toskeleton (Shen et al., 1998), positioning it ideally for neuronal CaMKII isoforms have markedly different a role in regulating actin-related morphology processes. roles in neuronal plasticity, with CaMKII␣ regulating Such actin targeting is isoform specific and not found synaptic strength and CaMKII␤ controlling the den-in the predominant neuronal CaMKII␣. While tubulin-dritic morphology and number of synapses. based cytoskeletal structures are key components of the main axonal and dendritic branches, most of the Introduction cytoskeletal structures in growth cones and extending dendritic processes are driven by actin polymerization One of the remarkable features of many CNS neurons (reviewed by …