Ror2-cytoskeleton interactions in morphogenesis

形态发生运动是协调的大量细胞运动，其在胚胎发育期间形成胚胎，并由不同的信号传导途径控制，包括非经典Wnt途径，如平面细胞极性或PCP途径。受体酪氨酸激酶Ror 2在脊椎动物PCP信号转导和形态发生中起重要作用。Ror 2功能丧失导致形态发生缺陷，例如缩短的体轴和短肢和尾（货车Bokhoven等人，2000; Oishi等人，2003年; Schambony和Wedlich，2007年）。除了其在Wnt信号传导途径中的作用之外，Ror 2已经显示通过结合细丝蛋白A来影响细胞形态（Nishita等人，2006; Nomachi等人，2008年）。然而，很少有人知道的Ror 2与细胞骨架的相互作用和它的贡献Ror 2的功能形态发生。协调细胞极性和调节细胞骨架重塑和细胞迁移是至关重要的形态发生运动。我们的初步数据显示，出乎意料的高百分比的细胞凋亡相关蛋白作为Ror 2的结合伙伴。这些结果表明细胞骨架相互作用对Ror 2功能的重要贡献。因此，Ror 2可能在形态发生中的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Ror 2和细胞骨架之间的生物化学，生物物理和功能相互作用。

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.