A Novel zf-MYND Protein, CHB-3, Mediates Guanylyl Cyclase Localization to Sensory Cilia and Controls Body Size of Caenorhabditis elegans

Autor: Victor L. Jensen, Laurie L. Molday, Phuong Anh T. Nguyen, Robert S. Molday, Katarzyna Kida, Oliver E. Blacque, Sharon L. Bishop-Hurley, Nathan J. Bialas, Donald L. Riddle, Michel R. Leroux
Jazyk: angličtina
Rok vydání: 2010
Předmět:
Cancer Research
lcsh:QH426-470
Cell Biology/Neuronal Signaling Mechanisms
Dauer larva
Biology
Flagellum
03 medical and health sciences
0302 clinical medicine
Intraflagellar transport
Ciliogenesis
Genetics
Animals
Humans
Cilia
Caenorhabditis elegans
Caenorhabditis elegans Proteins
Molecular Biology
Genetics (clinical)
Ecology
Evolution
Behavior and Systematics
Alleles
030304 developmental biology
0303 health sciences
Sequence Homology
Amino Acid
Cilium
Neuroscience/Sensory Systems
fungi
Epistasis
Genetic
Environmental exposure
biology.organism_classification
Cell biology
Transport protein
Protein Structure
Tertiary
Genetics and Genomics/Gene Function
Protein Transport
lcsh:Genetics
HEK293 Cells
Phenotype
Flagella
Guanylate Cyclase
Mutation
Genetics and Genomics/Gene Discovery
030217 neurology & neurosurgery
Research Article
Developmental Biology
Zdroj: PLoS Genetics, Vol 6, Iss 11, p e1001199 (2010)
PLoS Genetics
ISSN: 1553-7404
1553-7390
Popis: 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.
Author Summary C. elegans mutants that either fail to form or arrest development as dauer larvae, a stress-resistant lifestage, usually have defects in genes involved in evolutionarily conserved signaling pathways. In this study, we identified the gene mutated in daf-25 mutant strains, which inappropriately arrest as dauer larvae and are also defective in the sense of smell. The mammalian counterpart of DAF-25 is Ankmy2, a protein of unknown function that contains three ankyrin repeats and a zinc finger MYND domain, both of which are predicted to bind other protein(s). 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. We further demonstrate that mammalian Ankmy2 binds the retinal guanylyl cyclase GC1, suggesting a role for Ankmy2 in vision—which critically depends on cyclic GMP signal transduction—suggesting the potential involvement of Ankmy2 in human retinal disease, as well as other cilia-related diseases such as obesity.
Databáze: OpenAIRE
Externí odkaz: