Ror2-cytoskeleton interactions in morphogenesis

Ror2-细胞骨架在形态发生中的相互作用

• 批准号: 236616708
• 负责人: Professorin Dr. Alexandra Schambony
• 金额: --
• 依托单位: Lehrstuhl für Entwicklungsbiologie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2013
• 资助国家: 德国
• 起止时间: 2012-12-31 至 2016-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/236616708?language=en
• 关键词: Ror2; cytoskeleton; interactions; morphogenesis

Morphogenetic movements are coordinated mass cell movements, which shape an embryo during its development and are controlled by different signaling pathways including non-canonical Wnt-pathways such as the planar cell polarity or PCP pathway. The receptor tyrosine kinase Ror2 plays an important role in the regulation of PCP signaling and morphogenesis in vertebrates. Ror2 loss-of-function results in morphogenetic defects such as shortened body axis and short limbs and tails (van Bokhoven et al., 2000; Oishi et al., 2003; Schambony and Wedlich, 2007). In addition to its role in Wnt signaling pathways, Ror2 has been shown influence cell morphology by binding to Filamin A (Nishita et al., 2006; Nomachi et al., 2008). However, little is known about the interaction of Ror2 with the cytoskeleton and its contribution to Ror2 function in morphogenesis. Coordinating cell polarity and regulation of cytoskeleton remodelling and cell migration are crucial in morphogenetic movements. Our preliminary data revealed an unexpectedly high percentage of cytoskeleton-associated proteins as Ror2 binding partners. These results suggest a significant contribution of cytoskeleton interactions to Ror2 function. Thus, Ror2 could play a central role in the coordination of signal reception and cytoskeleton remodeling in morphogenesis. Here, we propose to study the biochemical, biophysical and functional interaction between Ror2 and the cytoskeleton in more detail using cell, tissue and in vivo model systems.

形态发生运动是协调的大量细胞运动，在胚胎发育过程中塑造胚胎，并受到不同信号通路的控制，包括非经典 Wnt 通路，例如平面细胞极性或 PCP 通路。受体酪氨酸激酶 Ror2 在脊椎动物 PCP 信号传导和形态发生的调节中发挥重要作用。 Ror2 功能丧失会导致形态发生缺陷，例如体轴缩短、四肢和尾巴变短（van Bokhoven 等，2000；Oishi 等，2003；Schambony 和 Wedlich，2007）。除了在 Wnt 信号通路中发挥作用外，Ror2 还被证明可以通过与 Filamin A 结合来影响细胞形态（Nishita 等人，2006；Nomachi 等人，2008）。然而，人们对 Ror2 与细胞骨架的相互作用及其对 Ror2 形态发生功能的贡献知之甚少。协调细胞极性以及细胞骨架重塑和细胞迁移的调节对于形态发生运动至关重要。我们的初步数据显示，作为 Ror2 结合伴侣的细胞骨架相关蛋白的比例出人意料地高。这些结果表明细胞骨架相互作用对 Ror2 功能有显着贡献。因此，Ror2可以在形态发生中信号接收和细胞骨架重塑的协调中发挥核心作用。在这里，我们建议使用细胞、组织和体内模型系统更详细地研究 Ror2 和细胞骨架之间的生化、生物物理和功能相互作用。