Abstract
Ciliopathies are pleiotropic and genetically heterogeneous disorders caused by defective development and function of the primary cilium. Bardet-Biedl syndrome (BBS) proteins localize to the base of cilia and undergo intraflagellar transport, and the loss of their functions leads to a multisystemic ciliopathy. Here we report the identification of mutations in guanylate cyclases (GCYs) as modifiers of Caenorhabditis elegans bbs endophenotypes. The loss of GCY-35 or GCY-36 results in suppression of the small body size, developmental delay, and exploration defects exhibited by multiple bbs mutants. Moreover, an effector of cGMP signalling, a cGMP-dependent protein kinase, EGL-4, also modifies bbs mutant defects. We propose that a misregulation of cGMP signalling, which underlies developmental and some behavioural defects of C. elegans bbs mutants, may also contribute to some BBS features in other organisms.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Animals, Genetically Modified
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Bardet-Biedl Syndrome / genetics*
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Bardet-Biedl Syndrome / metabolism
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Body Size / genetics
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Caenorhabditis elegans / genetics*
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Caenorhabditis elegans Proteins / genetics*
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Caenorhabditis elegans Proteins / metabolism
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Cilia / genetics
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Cilia / metabolism
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Cyclic GMP / genetics
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Cyclic GMP / metabolism
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Cyclic GMP-Dependent Protein Kinases / genetics*
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Cyclic GMP-Dependent Protein Kinases / metabolism
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Disease Models, Animal
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Guanylate Cyclase / genetics*
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Guanylate Cyclase / metabolism
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Humans
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Mutation
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Nerve Tissue Proteins / genetics*
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Nerve Tissue Proteins / metabolism
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Phenotype
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Protein Transport / genetics
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Sensory Receptor Cells / metabolism
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Signal Transduction / genetics
Substances
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Caenorhabditis elegans Proteins
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Nerve Tissue Proteins
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osm-12 protein, C elegans
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Cyclic GMP-Dependent Protein Kinases
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EGL-4 protein, C elegans
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GCY-35 protein, C elegans
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GCY-36 protein, C elegans
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Guanylate Cyclase
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Cyclic GMP