Strochlic Laure, Dwivedy Asha, van Horck Francisca P G, Falk Julien, Holt Christine E
Department of Physiology, Development and Neuroscience, Anatomy Building, University of Cambridge, Downing Street, Cambridge CB2 3DY, UK.
Development. 2008 Jan;135(2):333-42. doi: 10.1242/dev.009563. Epub 2007 Dec 12.
Sphingosine 1-phosphate (S1P), a lysophospholipid, plays an important chemotactic role in the migration of lymphocytes and germ cells, and is known to regulate aspects of central nervous system development such as neurogenesis and neuronal migration. Its role in axon guidance, however, has not been examined. We show that sphingosine kinase 1, an enzyme that generates S1P, is expressed in areas surrounding the Xenopus retinal axon pathway, and that gain or loss of S1P function in vivo causes errors in axon navigation. Chemotropic assays reveal that S1P elicits fast repulsive responses in retinal growth cones. These responses require heparan sulfate, are sensitive to inhibitors of proteasomal degradation, and involve RhoA and LIM kinase activation. Together, the data identify downstream components that mediate S1P-induced growth cone responses and implicate S1P signalling in axon guidance.
1-磷酸鞘氨醇（S1P）是一种溶血磷脂，在淋巴细胞和生殖细胞迁移中发挥重要的趋化作用，并且已知其可调节中枢神经系统发育的多个方面，如神经发生和神经元迁移。然而，其在轴突导向中的作用尚未得到研究。我们发现，生成S1P的酶鞘氨醇激酶1在非洲爪蟾视网膜轴突通路周围区域表达，并且体内S1P功能的获得或丧失会导致轴突导航错误。趋化性分析表明，S1P在视网膜生长锥中引发快速排斥反应。这些反应需要硫酸乙酰肝素，对蛋白酶体降解抑制剂敏感，并且涉及RhoA和LIM激酶激活。总之，这些数据确定了介导S1P诱导的生长锥反应的下游成分，并表明S1P信号传导参与轴突导向。
