β-arrestins – scaffolds and signalling elements essential for WNT/Frizzled signalling pathways?

β-arrestins were originally identified as negative regulators of G protein-coupled receptor signalling. Recent studies have revealed that β-arrestins serve as intracellular scaffolds and signalling intermediates. Their diverse functions in intracellular signalling pathways provide mechanisms for achieving signal specificity that might be attacked for pharmacological intervention. Here, we summarize the importance of β-arrestin function for WNT [wingless (from Drosophila) and the oncogene int-1]/Frizzled (FZD) signalling. WNTs are secreted lipoglycoproteins that act through the seven transmembrane-spanning receptors of the FZD family. It recently became evident that β-arrestins are required for cellular communication by means of WNTs and FZDs both in cellular systems and in vivo. Although the overall importance of arrestin for WNT/FZD signalling remains obscure, interaction with the central phosphoprotein Dishevelled and the endocytic machinery implicates β-arrestin as a determinant of WNT signalling specificity, a mediator of WNT/FZD desensitization and a regulator of signalling compartmentation.This article is part of a themed section on Molecular Pharmacology of GPCR. To view the editorial for this themed section visit http://dx.doi.org/10.1111/j.1476-5381.2010.00695.x     

RYK在小鼠皮质脊髓束神经通路发育过程中的表达变化

目的观察RYK在皮质脊髓束发育投射通路中的表达情况,为进一步研究RYK在其中的功能提供重要线索。方法通过原位杂交和免疫荧光组织化学法,分别检测了E14.5、E16、E18.5和出生后P3、P5、P7等不同时间点RYK在小鼠大脑运动皮层和皮质脊髓束神经通路中的表达情况。结果RYK的表达出现在胚胎E18.5 d运动皮层神经元中,到P0时逐渐增强并表达在脑内投射的皮质脊髓束神经通路,从P0~P5,RYK持续表达在皮质脊髓束在脑内和脊髓的整个神经通路上,而后逐渐减弱。结论RYK的表达与皮质脊髓束神经通路在脊髓中的发育投射有密切关系。