title: Jararhagin, a snake venom metalloprotease-disintegrin, activates the Rac1 GTPase and stimulates neurite outgrowth in neuroblastoma cells.
abstract: It has been shown previously that the snake venom metalloprotease-disintegrin jararhagin stimulates cell migration and cytoskeletal rearrangement, independently of its effects on cellular adhesion but possibly associated with the activation of small GTP-binding proteins from the Rho family [Costa, E.P., Santos, M.F., 2004. Toxicon 44(8), 861-870.] Here we show that jararhagin stimulates spreading, actin dynamics and neurite outgrowth in neuroblastoma cells, and that this effect is accompanied by the translocation of the Rac1 small GTPase to the membrane fraction, suggesting its activation. Stimulation of neurite outgrowth was observed within minutes and was dependent on the proteolytic activity of the toxin. These results suggest that jararhagin may stimulate neuronal differentiation, being a potential tool for neuronal regeneration studies.
authors.affiliation: Department of Cell and Developmental Biology, Institute of Biomedical Sciences, University of São Paulo, Av. Prof. Lineu Prestes 1524, São Paulo, SP 05508-000, Brazil.
authors.forename: Erica Pereira
authors.initials: EP
authors.lastname: Costa
authors.forename: Carolina Beltrame
authors.initials: CB
authors.lastname: Del Debbio
authors.forename: Leandro Carrijo
authors.initials: LC
authors.lastname: Cintra
authors.forename: Luciano
authors.initials: L
authors.lastname: da Fontoura Costa
authors.forename: Dânia Emi
authors.initials: DE
authors.lastname: Hamassaki
authors.forename: Marinilce Fagundes
authors.initials: MF
authors.lastname: Santos
mesh_terms: D000818:Animals; D017837:Bothrops / Q000502:physiology*; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D003435:Crotalid Venoms / Q000633:toxicity*; D008666:Metalloendopeptidases / Q000633:toxicity*; D018613:Microscopy, Confocal; D016501:Neurites / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D009447:Neuroblastoma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D010975:Platelet Aggregation Inhibitors / Q000633:toxicity*; D020830:rac1 GTP-Binding Protein / Q000378:metabolism*; D000097146:Bothrops jararaca Venom
chemical_list: D003435:Crotalid Venoms; D008666:Metalloendopeptidases; D010975:Platelet Aggregation Inhibitors; D020830:rac1 GTP-Binding Protein; D000097146:Bothrops jararaca Venom