CGC Bibliography Paper 5235
Regulated disruption of inositol 1,4,5-trisphosphate signaling in Caenorhabditis elegans reveals new functions in feeding and embryogenesis.
Walker DS,
Gower NJD,
Ly S,
Bradley GL,
Baylis HA
- Medline:
- 11950942
- Citation:
- Molecular Biology of the Cell 13: 1329-1337 2002
- Type:
- ARTICLE
- Genes:
- dec-4 elt-2 itr-1
- Abstract:
- Inositol 1,4,5-trisphosphate (IP3) is an important second messenger in animal cells and is central to a wide range of cellular responses. The major intracellular activity of IP3 is to regulate release of Ca2+ from intracellular stores through IP3 receptors (IP(3)Rs). We describe a system for the transient disruption of IP3 signaling in the model organism Caenorhabditis elegans. The IP3 binding domain of the C. elegans IP3R, ITR-1, was expressed from heat shock-induced promoters in live animals. This results in a dominant-negative effect caused by the overexpressed IP3 binding domain acting as an IP3 "sponge." Disruption of IP3 signaling resulted in disrupted defecation, a phenotype predicted by previous genetic studies. This approach also identified two new IP3-mediated processes. First, the up-regulation of pharyngeal pumping in response to food is dependent on IP3 signaling. RNA-mediated interference studies and analysis of itr-1 mutants show that this process is also IP3R dependent. Second, the tissue-specific expression of the dominant-negative construct enabled us to circumvent the sterility associated with loss Of IP3 signaling through the IP3R and thus determine that IP3-mediated signaling is required for multiple steps in embryogenesis, including cytokinesis and gastrulation.