Jararhagin, a snake venom metalloprotease-disintegrin, activates the Rac1 GTPase and stimulates neurite outgrowth in neuroblastoma cells

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 potential tool for neuronal regeneration studies. (C) 2008 Elsevier Ltd. All rights reserved.

FAPESP[01/09047-2]

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

FAPESP[05/00587-5]

FAPESP[06157508-2]

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

CNPq[301303/06-1]

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

CNPq[475074/2007-6]

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

CNPq[476763/2007-0]

CAPES

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)