Stay imaging shown that XAV939 remedy did not induce an noticeable adjust in the development fee of dendritic spines but appreciably diminished their Amcasertib elimination fee. Still left panels: representative photographs showing spine morphology in cultured neurons. Proper panels: quantitative outcomes of backbone formation/elimination price. Scale bar: ten m 17318-31-9 Student’s t-take a look at, n = 21, p < 0.001.results suggest that Axin preferentially acts through the small Rho-GTPase Cdc42 in dendritic spine morphogenesis, which is concordant with the report that glutamate uncaging-induced Cdc42 activation and spine growth are diminished by the CaMKII inhibitors KN62 and AIP2 . Axin may function as a scaffold to anchor CaMKII and restrict the local activation of Cdc42 within the dendritic spines . In addition to the structural plasticity of dendritic spines, CaMKII regulates the phosphorylation of the neurotransmitter receptor subunit GluA1 at Ser831, an important modification for receptor trafficking to the synapse and its conductance . Stabilizing endogenous Axin augments Ser831 phosphorylation, supporting the idea that Axin provides a docking site for CaMKII to potentiate synaptic functions. Understanding the interaction domains of Axin and CaMKII as well as their regulatory mechanisms will be important for understanding the scaffolding role of Axin in the structural and functional changes of synapses. On the other hand, Axin-SCAM interaction provides an alternative pathway by which the AMPA receptor can dock at synapses via stargazing [23, 24], providing a possible molecular basis that underlies the action of Axin in stabilizing synaptic neurotransmitter receptors. Small Rho-GTPases such as Cdc42, Rac1, and RhoA are believed to play important roles in morphological and functional changes of dendritic spines by modulating the balance between actin monomers and filaments . As a downstream effector of Axin, the activity of Cdc42 is tightly controlled by GEFs such as intersectin1 and – PIX, whose regulations of dendritic spine morphology are well characterized . However, neither the GEF nor the counteracting GAP that directly associates with Axin has been identified. Rac/Cdc42-specific GEF -PIX is a candidate component in the Axin complex through anchorage via -catenin and cadherin .