@article {Ben-GigiENEURO.0078-14.2015, author = {Liat Ben-Gigi and Sahar Sweetat and Elazar Besser and Yakov Fellig and Thorsten Wiederhold and Roberto D. Polakiewicz and Oded Behar}, title = {Astrogliosis induced by brain injury is regulated by Sema4B phosphorylation}, elocation-id = {ENEURO.0078-14.2015}, year = {2015}, doi = {10.1523/ENEURO.0078-14.2015}, publisher = {Society for Neuroscience}, abstract = {Injury to the central nervous system (CNS) induces astrogliosis, an astrocyte-mediated response that has both beneficial and detrimental impact 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. Significance Statement: Astrocyte activation plays a critical role in response to CNS trauma. Following CNS injury, astrogliosis has the beneficial effect of restricting tissue damage, but it also limits neuronal regeneration. That modulation of astrogliosis may improve neuronal regeneration is a widely held view. However, the cellular and molecular mechanisms underlying astrogliosis are not fully characterized. Here, we identify the involvement of an unexpected protein, Sema4B, a transmembrane member of the semaphorin family of proteins, in modulating astrocyte activation and proliferation in the aftermath of CNS injury. Although to date Sema4B has been shown to function as a ligand, our present results in astrocytes are more consistent with its function as a receptor or as a signaling molecule.}, URL = {https://www.eneuro.org/content/early/2015/05/15/ENEURO.0078-14.2015}, eprint = {https://www.eneuro.org/content/early/2015/05/15/ENEURO.0078-14.2015.full.pdf}, journal = {eNeuro} }