Stay imaging demonstrated that XAV939 therapy did not induce an apparent modify in the formation fee of dendritic spines but significantly decreased their elimination price

Stay imaging demonstrated that XAV939 buy 56-25-7 treatment method did not induce an apparent adjust in the formation D-JNKI-1 charge of dendritic spines but significantly decreased their elimination rate. Still left panels: representative photographs displaying backbone morphology in cultured neurons. Appropriate panels: quantitative final results of backbone formation/elimination charge. Scale bar: ten m Student’s t-examination, 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 [19]. Axin may function as a scaffold to anchor CaMKII and restrict the local activation of Cdc42 within the dendritic spines [19]. 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 [22]. 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 [25]. 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 [268]. 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 [27].

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