GLOBIN-5-dependent O2 responses are regulated by PDL- 1/PrBP that targets prenylated soluble guanylate cyclases to dendritic endings

Einav Gross, Zoltan Soltesz, Shigekazu Oda, Veronica Zelmanovich, Zohar Abergel, Mario de Bono*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

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 Ca2+ 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/PDE6÷ protein. In mammals, PDE6÷ 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.

Original languageAmerican English
Pages (from-to)16726-16738
Number of pages13
JournalJournal of Neuroscience
Volume34
Issue number50
DOIs
StatePublished - 10 Dec 2014

Bibliographical note

Publisher Copyright:
© 2014 Gross et al.

Keywords

  • C. elegans
  • Globin
  • Hypoxia
  • Oxygen sensing
  • Prenyl binding protein
  • Soluble guanylate cyclase

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