Mutations in a guanylate cyclase GCY-35/GCY-36 modify Bardet-Biedl syndrome-associated phenotypes in Caenorhabditis elegans.
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.
The Program in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Canada.
Calvin A
CA
Mok
Michael P
MP
Healey
Tanvi
T
Shekhar
Michel R
MR
Leroux
Elise
E
Héon
Mei
M
Zhen
D000818:Animals; D030801:Animals, Genetically Modified; D020788:Bardet-Biedl Syndrome / Q000235:genetics* / Q000378:metabolism; D049628:Body Size / Q000235:genetics; D017173:Caenorhabditis elegans / Q000235:genetics*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics* / Q000378:metabolism; D002923:Cilia / Q000235:genetics / Q000378:metabolism; D006152:Cyclic GMP / Q000235:genetics / Q000378:metabolism; D017869:Cyclic GMP-Dependent Protein Kinases / Q000235:genetics* / Q000378:metabolism; D004195:Disease Models, Animal; D006162:Guanylate Cyclase / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D010641:Phenotype; D021381:Protein Transport / Q000235:genetics; D011984:Sensory Receptor Cells / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics
D029742:Caenorhabditis elegans Proteins; D009419:Nerve Tissue Proteins; C502669:osm-12 protein, C elegans; D017869:Cyclic GMP-Dependent Protein Kinases; C470349:EGL-4 protein, C elegans; C488166:GCY-35 protein, C elegans; C511349:GCY-36 protein, C elegans; D006162:Guanylate Cyclase; D006152:Cyclic GMP