title: GLOBIN-5-dependent O2 responses are regulated by PDL-1/PrBP that targets prenylated soluble guanylate cyclases to dendritic endings.
abstract: Aerobic animals constantly monitor and adapt to changes in O2 levels. The molecular mechanisms involved in sensing O2 are, however, incompletely understood. Previous studies showed that a hexacoordinated globin called GLB-5 tunes the dynamic range of O2-sensing neurons in natural C. elegans isolates, but is defective in the N2 lab reference strain (McGrath et al., 2009; Persson et al., 2009). GLB-5 enables a sharp behavioral switch when O2 changes between 21 and 17%. Here, we show that GLB-5 also confers rapid behavioral and cellular recovery from exposure to hypoxia. Hypoxia reconfigures O2-evoked Ca(2+) responses in the URX O2 sensors, and GLB-5 enables rapid recovery of these responses upon re-oxygenation. Forward genetic screens indicate that GLB-5's effects on O2 sensing require PDL-1, the C. elegans ortholog of mammalian PrBP/PDE6δ protein. In mammals, PDE6δ regulates the traffic and activity of prenylated proteins (Zhang et al., 2004; Norton et al., 2005). PDL-1 promotes localization of GCY-33 and GCY-35, atypical soluble guanylate cyclases that act as O2 sensors, to the dendritic endings of URX and BAG neurons, where they colocalize with GLB-5. Both GCY-33 and GCY-35 are predicted to be prenylated. Dendritic localization is not essential for GCY-35 to function as an O2 sensor, but disrupting pdl-1 alters the URX neuron's O2 response properties. Functional GLB-5 can restore dendritic localization of GCY-33 in pdl-1 mutants, suggesting GCY-33 and GLB-5 are in a complex. Our data suggest GLB-5 and the soluble guanylate cyclases operate in close proximity to sculpt O2 responses.
authors.affiliation: The Hebrew University of Jerusalem, Faculty of Medicine, IMRIC, Jerusalem, 91120 Israel and MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, United Kingdom debono@mrc-lmb.cam.ac.uk einavg@ekmd.huji.ac.il.
authors.forename: Einav
authors.identifier: http://orcid.org/0000-0003-4050-8784
authors.initials: E
authors.lastname: Gross
authors.affiliation: MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, United Kingdom.
authors.forename: Zoltan
authors.initials: Z
authors.lastname: Soltesz
authors.affiliation: MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, United Kingdom.
authors.forename: Shigekazu
authors.initials: S
authors.lastname: Oda
authors.affiliation: The Hebrew University of Jerusalem, Faculty of Medicine, IMRIC, Jerusalem, 91120 Israel and.
authors.forename: Veronica
authors.initials: V
authors.lastname: Zelmanovich
authors.affiliation: The Hebrew University of Jerusalem, Faculty of Medicine, IMRIC, Jerusalem, 91120 Israel and.
authors.forename: Zohar
authors.identifier: http://orcid.org/0000-0003-3115-5913
authors.initials: Z
authors.lastname: Abergel
authors.affiliation: MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, United Kingdom debono@mrc-lmb.cam.ac.uk einavg@ekmd.huji.ac.il.
authors.forename: Mario
authors.initials: M
authors.lastname: de Bono
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins / Q000502:physiology*; D003712:Dendrites / Q000201:enzymology*; D005914:Globins / Q000502:physiology*; D006162:Guanylate Cyclase / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism*; D061026:Programmed Cell Death 1 Receptor / Q000502:physiology*; D017368:Protein Prenylation / Q000502:physiology*; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D000071756:Soluble Guanylyl Cyclase
chemical_list: D029742:Caenorhabditis elegans Proteins; C541176:GLB-5 protein, C elegans; D061026:Programmed Cell Death 1 Receptor; D018160:Receptors, Cytoplasmic and Nuclear; D005914:Globins; D006162:Guanylate Cyclase; D000071756:Soluble Guanylyl Cyclase; D010100:Oxygen
keywords: C. elegans; globin; hypoxia; oxygen sensing; prenyl binding protein; soluble guanylate cyclase