Abstract
In harsh conditions, Caenorhabditis elegans arrests development to enter a non-aging, resistant diapause state called the dauer larva. Olfactory sensation modulates the TGF-β and insulin signaling pathways to control this developmental decision. Four mutant alleles of daf-25 (abnormal DAuer Formation) were isolated from screens for mutants exhibiting constitutive dauer formation and found to be defective in olfaction. The daf-25 dauer phenotype is suppressed by daf-10/IFT122 mutations (which disrupt ciliogenesis), but not by daf-6/PTCHD3 mutations (which prevent environmental exposure of sensory cilia), implying that DAF-25 functions in the cilia themselves. daf-25 encodes the C. elegans ortholog of mammalian Ankmy2, a MYND domain protein of unknown function. Disruption of DAF-25, which localizes to sensory cilia, produces no apparent cilia structure anomalies, as determined by light and electron microscopy. Hinting at its potential function, the dauer phenotype, epistatic order, and expression profile of daf-25 are similar to daf-11, which encodes a cilium-localized guanylyl cyclase. Indeed, we demonstrate that DAF-25 is required for proper DAF-11 ciliary localization. Furthermore, the functional interaction is evolutionarily conserved, as mouse Ankmy2 interacts with guanylyl cyclase GC1 from ciliary photoreceptors. The interaction may be specific because daf-25 mutants have normally-localized OSM-9/TRPV4, TAX-4/CNGA1, CHE-2/IFT80, CHE-11/IFT140, CHE-13/IFT57, BBS-8, OSM-5/IFT88, and XBX-1/D2LIC in the cilia. Intraflagellar transport (IFT) (required to build cilia) is not defective in daf-25 mutants, although the ciliary localization of DAF-25 itself is influenced in che-11 mutants, which are defective in retrograde IFT. In summary, we have discovered a novel ciliary protein that plays an important role in cGMP signaling by localizing a guanylyl cyclase to the sensory organelle.
Highlights
The dauer larva of Caenorhabditis elegans is an alternate third larval stage where a stress resistant, non-aging life plan is adopted in harsh environmental conditions [1]
We identified the gene mutated in daf-25 mutant strains, which inappropriately arrest as dauer larvae and are defective in the sense of smell
We show that DAF-25/Ankmy2 is required for the proper localization of a membrane-bound guanylyl cyclase—a class of protein that functions in cyclic GMP signaling—to cilia, which are conserved sensory organelles
Summary
The dauer larva of Caenorhabditis elegans is an alternate third larval stage where a stress resistant, non-aging life plan is adopted in harsh environmental conditions [1]. Dauer larvae disperse and will resume development when conditions improve. The study of dauer formation has elucidated a complex gene network used to control the decision to go into diapause [2]. The dauer pathway includes well-recognized members in the canonical TGF-b (Transforming Growth Factor-Beta) and Insulin/Insulin-like signaling (IIS) pathways, as well as proteins affecting olfactory reception, neuron depolarization and peptide hormone secretion. Many mutants isolated as dauer formation defective (Daf-d) or constitutive (Daf-c) have revealed the key signaling components [2]. We identify DAF-25, a novel member of the olfactory signaling pathway that is associated with cGMP signaling—a signal transduction pathway with established links to cilia [3]. We show that the mammalian ortholog, Ankmy, is expressed in ciliary photoreceptors and interacts with a guanylate cyclase (GC1), as predicted from the C. elegans results
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