Department of Developmental Biology and Cancer Research, Institute of Medical Research Israel-Canada (IMRIC)] , Faculty of Medicine , The Hebrew University , Jerusalem 91120, Israel.
Neuropathology Unit, Department of Pathology, Hadassah Medical Center , The Hebrew University , Jerusalem 91120, Israel.
eNeuro. 2015 May 25;2(3). doi: 10.1523/ENEURO.0078-14.2015. eCollection 2015 May-Jun.
Injury to the CNS induces astrogliosis, an astrocyte-mediated response that has both beneficial and detrimental impacts on surrounding neural and non-neural cells. The precise signaling events underlying astrogliosis are not fully characterized. Here, we show that astrocyte activation was altered and proliferation was reduced in Semaphorin 4B (Sema4B)-deficient mice following injury. Proliferation of cultured Sema4B(-/-) astrocytes was also significantly reduced. In contrast to its expected role as a ligand, the Sema4B ectodomain was not able to rescue Sema4B(-/-) astrocyte proliferation but instead acted as an antagonist against Sema4B(+/-) astrocytes. Furthermore, the effects of Sema4B on astrocyte proliferation were dependent on phosphorylation of the intracellular domain at Ser825. Our results suggest that Sema4B functions as an astrocyte receptor, defining a novel signaling pathway that regulates astrogliosis after CNS injury.
中枢神经系统损伤会诱导星形胶质细胞增生，这是一种由星形胶质细胞介导的反应，对周围的神经和非神经细胞既有有益影响，也有有害影响。星形胶质细胞增生的确切信号事件尚未完全阐明。在这里，我们发现，在损伤后，Semaphorin 4B（Sema4B）缺陷型小鼠的星形胶质细胞激活被改变，增殖减少。培养的 Sema4B（-/-）星形胶质细胞的增殖也显著减少。与作为配体的预期作用相反，Sema4B 外显子不能挽救 Sema4B（-/-）星形胶质细胞的增殖，反而对 Sema4B（+/-）星形胶质细胞起拮抗作用。此外，Sema4B 对星形胶质细胞增殖的影响依赖于 Ser825 处细胞内结构域的磷酸化。我们的结果表明，Sema4B 作为星形胶质细胞受体发挥作用，定义了一条新的信号通路，调节中枢神经系统损伤后的星形胶质细胞增生。
