RRC ID 46293
Author Mok CA, Healey MP, Shekhar T, Leroux MR, Héon E, Zhen M.
Title Mutations in a guanylate cyclase GCY-35/GCY-36 modify Bardet-Biedl syndrome-associated phenotypes in Caenorhabditis elegans.
Journal PLoS Genet
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.
Volume 7(10)
Pages e1002335
Published 2011-10-1
DOI 10.1371/journal.pgen.1002335
PII PGENETICS-D-11-01033
PMID 22022287
PMC PMC3192831
MeSH Animals Animals, Genetically Modified Bardet-Biedl Syndrome / genetics* Bardet-Biedl Syndrome / metabolism Body Size / genetics Caenorhabditis elegans / genetics* Caenorhabditis elegans Proteins / genetics* Caenorhabditis elegans Proteins / metabolism Cilia / genetics Cilia / metabolism Cyclic GMP / genetics Cyclic GMP / metabolism Cyclic GMP-Dependent Protein Kinases / genetics* Cyclic GMP-Dependent Protein Kinases / metabolism Disease Models, Animal Guanylate Cyclase / genetics* Guanylate Cyclase / metabolism Humans Mutation Nerve Tissue Proteins / genetics* Nerve Tissue Proteins / metabolism Phenotype Protein Transport / genetics Sensory Receptor Cells / metabolism Signal Transduction / genetics
IF 5.175
Times Cited 11
WOS Category GENETICS & HEREDITY
Resource
C.elegans tm1653 tm901 tm2411 tm4300 tm2669 tm1449 tm2816 tm2364 tm324