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. © 2011 mok et al.