cyclic-gmp and Bardet-Biedl-Syndrome

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.

Topics: Animals; Animals, Genetically Modified; Bardet-Biedl Syndrome; Body Size; Caenorhabditis elegans; Caenorhabditis elegans Proteins; Cilia; Cyclic GMP; Cyclic GMP-Dependent Protein Kinases; Disease Models, Animal; Guanylate Cyclase; Humans; Mutation; Nerve Tissue Proteins; Phenotype; Protein Transport; Sensory Receptor Cells; Signal Transduction