title: A Conserved GEF for Rho-Family GTPases Acts in an EGF Signaling Pathway to Promote Sleep-like Quiescence in Caenorhabditis elegans.
abstract: Sleep is evolutionarily conserved and required for organism homeostasis and survival. Despite this importance, the molecular and cellular mechanisms underlying sleep are not well understood. Caenorhabditis elegans exhibits sleep-like behavioral quiescence and thus provides a valuable, simple model system for the study of cellular and molecular regulators of this process. In C. elegans, epidermal growth factor receptor (EGFR) signaling is required in the neurosecretory neuron ALA to promote sleep-like behavioral quiescence after cellular stress. We describe a novel role for VAV-1, a conserved guanine nucleotide exchange factor (GEF) for Rho-family GTPases, in regulation of sleep-like behavioral quiescence. VAV-1, in a GEF-dependent manner, acts in ALA to suppress locomotion and feeding during sleep-like behavioral quiescence in response to cellular stress. Additionally, VAV-1 activity is required for EGF-induced sleep-like quiescence and normal levels of EGFR and secretory dense core vesicles in ALA. Importantly, the role of VAV-1 in promoting cellular stress-induced behavioral quiescence is vital for organism health because VAV-1 is required for normal survival after cellular stress.
authors.affiliation: Center for Cell Biology and Cancer Research, Albany Medical College, New York 12208.
authors.forename: Amanda L
authors.initials: AL
authors.lastname: Fry
authors.affiliation: Center for Cell Biology and Cancer Research, Albany Medical College, New York 12208.
authors.forename: Jocelyn T
authors.initials: JT
authors.lastname: Laboy
authors.affiliation: Department of Neuroscience, Brown University, Providence, Rhode Island 02912.
authors.forename: Huiyan
authors.initials: H
authors.lastname: Huang
authors.affiliation: Department of Neuroscience, Brown University, Providence, Rhode Island 02912.
authors.forename: Anne C
authors.initials: AC
authors.lastname: Hart
authors.affiliation: Center for Cell Biology and Cancer Research, Albany Medical College, New York 12208 normank@mail.amc.edu.
authors.forename: Kenneth R
authors.initials: KR
authors.lastname: Norman
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D001522:Behavior, Animal / Q000502:physiology; D017173:Caenorhabditis elegans / Q000235:genetics / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000502:physiology*; D004815:Epidermal Growth Factor / Q000502:physiology; D066246:ErbB Receptors / Q000502:physiology; D005247:Feeding Behavior / Q000502:physiology; D007395:Interneurons / Q000502:physiology*; D008124:Locomotion / Q000502:physiology*; D016297:Mutagenesis, Site-Directed; D051567:Proto-Oncogene Proteins c-vav / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction; D013312:Stress, Physiological
chemical_list: D029742:Caenorhabditis elegans Proteins; D051567:Proto-Oncogene Proteins c-vav; C505656:VAV-1 protein, C elegans; C075912:Lin-3 protein, C elegans; D004815:Epidermal Growth Factor; D066246:ErbB Receptors
keywords: Caenorhabditis elegans; Vav; behavioral quiescence; sleep