From neuronal activity to the actin cytoskeleton: a role for CaMKKs and betaPIX in spine morphogenesis

Abstract

Electrical activity plays a crucial role in neuronal circuit assembly. Activation of NMDA receptors induces the elevation of intracellular calcium, resulting in the modulation of calcium-calmodulin-dependent protein kinases (CaMKs). The CaMK pathway regulates synaptogenesis by driving the formation of dendritic spines. However, the molecular effectors downstream of this pathway have remained poorly defined. In this issue of Neuron, Saneyoshi et al. identify a new signaling complex containing CaMKK/CaMKI/betaPIX/Rac that regulates the morphogenesis of spines in an activity-dependent manner.

Figure 1. Electrical activity through a calcium dependent signalling pathway modulates spine formation

Upon NMDA receptor activation, the Ca²⁺/Calmodulin complex activates the βCAMKK/αCaMKI pathway that in turn phosphorylates βPIX resulting in Rac activation and spine morphogenesis. PAK, a downstream effector of Rac1, regulates the actin cytoskeleton during spine formation. A feedback loop through PAK could also regulate ßPIX activity.