PT - JOURNAL ARTICLE AU - Liat Ben-Gigi AU - Sahar Sweetat AU - Elazar Besser AU - Yakov Fellig AU - Thorsten Wiederhold AU - Roberto D. Polakiewicz AU - Oded Behar TI - Astrogliosis Induced by Brain Injury Is Regulated by Sema4B Phosphorylation AID - 10.1523/ENEURO.0078-14.2015 DP - 2015 May 01 TA - eneuro PG - ENEURO.0078-14.2015 VI - 2 IP - 3 4099 - http://www.eneuro.org/content/2/3/ENEURO.0078-14.2015.short 4100 - http://www.eneuro.org/content/2/3/ENEURO.0078-14.2015.full SO - eneuro2015 May 01; 2 AB - 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.