title: Astrogliosis Induced by Brain Injury Is Regulated by Sema4B Phosphorylation
abstract: 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.
authors.affiliation: Department of Developmental Biology and Cancer Research, Institute of Medical Research Israel-Canada (IMRIC)] , Faculty of Medicine , The Hebrew University , Jerusalem 91120, Israel.
authors.forename: Liat
authors.initials: L
authors.lastname: Ben-Gigi
authors.affiliation: Department of Developmental Biology and Cancer Research, Institute of Medical Research Israel-Canada (IMRIC)] , Faculty of Medicine , The Hebrew University , Jerusalem 91120, Israel.
authors.forename: Sahar
authors.initials: S
authors.lastname: Sweetat
authors.affiliation: Department of Developmental Biology and Cancer Research, Institute of Medical Research Israel-Canada (IMRIC)] , Faculty of Medicine , The Hebrew University , Jerusalem 91120, Israel.
authors.forename: Elazar
authors.initials: E
authors.lastname: Besser
authors.affiliation: Neuropathology Unit, Department of Pathology, Hadassah Medical Center , The Hebrew University , Jerusalem 91120, Israel.
authors.forename: Yakov
authors.initials: Y
authors.lastname: Fellig
authors.affiliation: Cell Signaling Technology , Inc. , Danvers, Massachusetts 01923.
authors.forename: Thorsten
authors.initials: T
authors.lastname: Wiederhold
authors.affiliation: Cell Signaling Technology , Inc. , Danvers, Massachusetts 01923.
authors.forename: Roberto D
authors.initials: RD
authors.lastname: Polakiewicz
authors.affiliation: Department of Developmental Biology and Cancer Research, Institute of Medical Research Israel-Canada (IMRIC)] , Faculty of Medicine , The Hebrew University , Jerusalem 91120, Israel.
authors.forename: Oded
authors.initials: O
authors.lastname: Behar
keywords: CNS injury; Sema4B; astrogliosis