Berger Birgit S, Acebron Sergio P, Herbst Jessica, Koch Stefan, Niehrs Christof
Division of Molecular Embryology, DKFZ-ZMBH Alliance, Heidelberg, Germany.
Division of Molecular Embryology, DKFZ-ZMBH Alliance, Heidelberg, Germany
EMBO Rep. 2017 May;18(5):712-725. doi: 10.15252/embr.201643585. Epub 2017 Mar 24.
Wnt/β-catenin signaling plays a key role in embryonic development, stem cell biology, and neurogenesis. However, the mechanisms of Wnt signal transmission, notably how the receptors are regulated, remain incompletely understood. Here we describe that the Parkinson's disease-associated receptor GPR37 functions in the maturation of the N-terminal bulky β-propellers of the Wnt co-receptor LRP6. GPR37 is required for Wnt/β-catenin signaling and protects LRP6 from ER-associated degradation via CHIP (carboxyl terminus of Hsc70-interacting protein) and the ATPase VCP GPR37 is highly expressed in neural progenitor cells (NPCs) where it is required for Wnt-dependent neurogenesis. We conclude that GPR37 is crucial for cellular protein quality control during Wnt signaling.
Wnt/β-连环蛋白信号通路在胚胎发育、干细胞生物学和神经发生中起关键作用。然而，Wnt信号转导的机制，尤其是受体如何被调节，仍未完全了解。在此我们描述帕金森病相关受体GPR37在Wnt共受体LRP6的N端大β-螺旋桨成熟中发挥作用。Wnt/β-连环蛋白信号通路需要GPR37，并且它通过CHIP（Hsc70相互作用蛋白的羧基末端）和ATP酶VCP保护LRP6免受内质网相关降解。GPR37在神经祖细胞（NPC）中高度表达，在Wnt依赖的神经发生中它是必需的。我们得出结论，GPR37在Wnt信号传导过程中对细胞蛋白质质量控制至关重要。
