Department of Molecular Cell Biology, Leiden University Medical Center, 2300 RC Leiden, The Netherlands.
Trends Neurosci. 2010 Feb;33(2):84-92. doi: 10.1016/j.tins.2009.11.005. Epub 2009 Dec 11.
Conserved Ryk transmembrane proteins, tyrosine kinase-related Wnt receptors, are important during neurogenesis, axon guidance and synaptogenesis. Here, we review the increasingly complex biology of the Wnt/Ryk pathway, emphasizing the mechanisms by which Ryks transduce or sometimes block the Wnt signal. Recent studies reveal that Wnts signal through Ryk via multiple mechanisms, including nuclear translocation of their intracellular domains and pathways employing Src Family Kinases and members of the canonical Wnt pathway. We also discuss reports indicating that Wnt/Ryk axon guidance roles are evolutionarily conserved and Wnt/Ryk interactions are required for motoneuron target selection and synaptogenesis at the neuromuscular junction. Recent findings that injury-induced Wnt/Ryk pathway activation inhibits axon regeneration underscore the importance of further understanding this novel pathway.
保守的 Ryk 跨膜蛋白，酪氨酸激酶相关的 Wnt 受体，在神经发生、轴突导向和突触发生过程中非常重要。在这里，我们回顾了 Wnt/Ryk 途径日益复杂的生物学特性，强调了 Ryks 转导或有时阻断 Wnt 信号的机制。最近的研究表明，Wnts 通过多种机制通过 Ryk 发出信号，包括其细胞内结构域的核易位以及使用 Src 家族激酶和经典 Wnt 途径成员的途径。我们还讨论了表明 Wnt/Ryk 轴突导向作用在进化上是保守的，并且 Wnt/Ryk 相互作用对于运动神经元靶选择和神经肌肉接头处的突触发生是必需的报告。最近发现，损伤诱导的 Wnt/Ryk 途径激活抑制轴突再生，这突显了进一步了解这一新途径的重要性。
