Guanine nucleotide exchange factor osg-1 confers functional aging via dysregulated rho signaling in caenorhabditis elegans neurons

Zhibing Duan, Federico Sesti

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

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 chal-lenges, 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.

Original languageEnglish (US)
Pages (from-to)487-496
Number of pages10
JournalGenetics
Volume199
Issue number2
DOIs
StatePublished - Feb 1 2014

All Science Journal Classification (ASJC) codes

  • Genetics

Keywords

  • Chemotaxis
  • Oxidative stress
  • Reactive oxygen species
  • Rho GTPase

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