Mutations in a Guanylate Cyclase GCY-35/GCY-36 Modify Bardet-Biedl Syndrome–Associated Phenotypes in Caenorhabditis elegans

The Program in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Canada.
PLoS Genetics (Impact Factor: 7.53). 10/2011; 7(10):e1002335. DOI: 10.1371/journal.pgen.1002335
Source: PubMed

ABSTRACT Author Summary
Bardet-Biedl syndrome (BBS) is a genetically heterogeneous, multisystemic disorder. Defects to the cilium, an evolutionarily conserved organelle, cause ciliopathies, a growing class of diseases that includes BBS. BBS proteins are involved in the vesicular transport of proteins to the cilium and in the process of intraflagellar transport. Here we show that, in addition to sensory defects, Caenorhabditis elegans bbs mutants exhibit reduced body size and delayed developmental timing. The reduced body size phenotype is not fully recapitulated by IFT mutants, suggesting that BBS proteins may have additional functions beyond bridging IFT motors. We further identified that the loss of function mutations in the soluble guanylate cyclase complex, GCY-35/GCY-36, results in a suppression of these defects. Interestingly, GCY-35/GCY-36 influences the body size through a cGMP-dependent protein kinase EGL-4 in a group of body cavity neurons. BBS proteins, on the other hand, function through a non-overlapping set of ciliated sensory neurons to influence cGMP signalling in the body cavity neurons. In conclusion, this study reveals a non-cell autonomous role for sensory cilia in regulating cGMP signalling during development. We propose that aberrant cGMP signalling, essential for a number of cellular processes, may also contribute to some ciliopathy features in other systems.

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Available from: Mei Zhen, May 24, 2015
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    • "Downstream of the ADF neurons, 5-HT signaling requires the function of the mod-1 5-HT-gated channel in the URX body cavity neurons. The URX neuron pair along with the AQR and PQR body cavity neurons are best known for their role in oxygen sensing and aerotaxis (Cheung et al., 2005; Gray et al., 2004) and, more recently, in body size regulation (Mok et al., 2011). "
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