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]CAPESCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES

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<p>The double vertical lines indicate the BovineHD0500032585 SNP position. Colored positions indicate flanking SNPs. There are 6 non-synonymous SNPs and 1 synonymous SNP (4^th column from left).</p

Mean frequency and standard deviation of the nearest Nelore SNPs within 50bp and 100bp size bins.

<p>Mean frequency and standard deviation of the nearest Nelore SNPs within 50bp and 100bp size bins.</p

Functional characterization of 3,183 SNP markers derived from the Illumina Bovine HD panel that consistently generated missing genotypes in the Nelore breed (SFNBs).

<p>Functional characterization of 3,183 SNP markers derived from the Illumina Bovine HD panel that consistently generated missing genotypes in the Nelore breed (SFNBs).</p

Frequency of missing genotypes in Nelore cattle in a total of 1,709 samples tested with the Illumina Bovine HD.

<p>Frequency of missing genotypes in Nelore cattle in a total of 1,709 samples tested with the Illumina Bovine HD.</p

Distribution of SFNBs across bovine chromosomes.

<p>Distribution of SFNBs across bovine chromosomes.</p

GO annotation of biological processes affected by genes that were identified by SFNBs from the Illumina Bovine HD panel.

<p>GO annotation of biological processes affected by genes that were identified by SFNBs from the Illumina Bovine HD panel.</p

Regions defined for obtaining estimates of genomic variation.

<p>P1 represents the 50bp Illumina probe target sequence. P2 corresponds to the 50bp adjacent to P1 on the distal side of the assayed SNP. S1 and S2 are symmetrical to P1 and P2, respectively.</p

Number of non-redundant SFNBs in regions flanking SNPs assayed in the Illumina Bovine HD panel (see S1 Table).

<p>Number of non-redundant SFNBs in regions flanking SNPs assayed in the Illumina Bovine HD panel (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0136035#pone.0136035.s001" target="_blank">S1 Table</a>).</p

Detailed information for 32 SNPs located within coding regions flanking SFNBs which resulted in non-synonymous substitutions.

<p>An extreme case of non-synonymous mutations in gene EP300. Large numbers of olfactory receptor genes were found to contain SNPs that result in non-synonymous substitutions.</p