Induction of neuronal apoptosis by Semaphorin3A-derived peptide

Collapsin-1/Semaphorin3A (Sema3A) belongs to the: secreted type III semapho rins family of axon guidance molecules with chemorepulsive activity, and is suggested to play a major role in navigating axonal networks throughout de velopment into their correct destinations. We have previously shown that se maphorins are mediators of neuronal apoptosis and can induce neuronal death in the absence of any other apoptotic trigger. We report here that exposur e of neuronal cells to a small conserved peptide derived from Sema3A initia tes an apoptotic death process. Administration of this peptide to cultured chick sympathetic and mouse cerebellar granule neurons caused a marked shri nkage of their axonal network and cell death, which was characterized as ap optotic, based on nuclear staining. Attenuation of neuronal cell death was obtained by treatment with antioxidants and by vascular endothelial growth factor. Survival of neurons exposed to this peptide increased by co-treatme nt with caspase inhibitors. Induction of apoptosis was specific to neuronal cells, similarly to that induced by the full-length Sema3A protein. Our fi ndings therefore suggest active participation of this conserved Serna3A-der ived peptide in semaphorin-induced neuronal death process. (C) 2000 Elsevie r Science B.V. All rights reserved.