title: Guanine nucleotide exchange factor OSG-1 confers functional aging via dysregulated Rho signaling in Caenorhabditis elegans neurons.
abstract: Rho signaling regulates a variety of biological processes, but whether it is implicated in aging remains an open question. Here we show that a guanine nucleotide exchange factor of the Dbl family, OSG-1, confers functional aging by dysregulating Rho GTPases activities in C. elegans. Thus, gene reporter analysis revealed widespread OSG-1 expression in muscle and neurons. Loss of OSG-1 gene function was not associated with developmental defects. In contrast, suppression of OSG-1 lessened loss of function (chemotaxis) in ASE sensory neurons subjected to conditions of oxidative stress generated during natural aging, by oxidative challenges, or by genetic mutations. RNAi analysis showed that OSG-1 was specific toward activation of RHO-1 GTPase signaling. RNAi further implicated actin-binding proteins ARX-3 and ARX-5, thus the actin cytoskeleton, as one of the targets of OSG-1/RHO-1 signaling. Taken together these data suggest that OSG-1 is recruited under conditions of oxidative stress, a hallmark of aging, and contributes to promote loss of neuronal function by affecting the actin cytoskeleton via altered RHO-1 activity.
authors.affiliation: Department of Neuroscience and Cell Biology, Robert Wood Johnson Medical School, Rutgers University, Piscataway, New Jersey 08854.
authors.forename: Zhibing
authors.initials: Z
authors.lastname: Duan
authors.affiliation: Department of Neuroscience and Cell Biology, Robert Wood Johnson Medical School, Rutgers University, Piscataway, New Jersey 08854 federico.sesti@rutgers.edu.
authors.forename: Federico
authors.initials: F
authors.lastname: Sesti
mesh_terms: D000375:Aging / Q000235:genetics*; D016229:Amyloid beta-Peptides / Q000235:genetics; D000818:Animals; D030801:Animals, Genetically Modified; D017173:Caenorhabditis elegans / Q000235:genetics* / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics* / Q000378:metabolism*; D002874:Chromosome Mapping; D003712:Dendrites / Q000378:metabolism; D015870:Gene Expression; D017930:Genes, Reporter; D056426:Genetic Loci; D006801:Humans; D008136:Longevity / Q000235:genetics; D009132:Muscles / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D018384:Oxidative Stress; D010641:Phenotype; D011485:Protein Binding; D015398:Signal Transduction; D020741:rho GTP-Binding Proteins / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; D029742:Caenorhabditis elegans Proteins; D020741:rho GTP-Binding Proteins
keywords: Rho GTPase; chemotaxis; oxidative stress; reactive oxygen species