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


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
Issue number50
StatePublished - 10 Dec 2014

Bibliographical note

Publisher Copyright:
© 2014 Gross et al.


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


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