A Direct Interaction between IP3 Receptors and Myosin II Regulates IP3 Signaling in C. elegans

AbstractMolecular and physiological studies of cells implicate interactions between the cytoskeleton and the intracellular calcium signalling machinery as an important mechanism for the regulation of calcium signalling [1–11]. However, little is known about the functions of such mechanisms in animals. A key component of the calcium signalling network is the intracellular release of calcium in response to the production of the second messenger inositol 1,4,5-trisphosphate (IP3), mediated by the IP3 receptor (IP3R) [12–14]. We show that C. elegans IP3Rs, encoded by the gene itr-1, interact directly with myosin II. The interactions between two myosin proteins, UNC-54 and MYO-1, and ITR-1 were identified in a yeast two-hybrid screen and subsequently confirmed in vivo and in vitro. We defined the interaction sites on both the IP3R and MYO-1. To test the effect of disrupting the interaction in vivo we overexpressed interacting fragments of both proteins in C. elegans. This decreased the animal's ability to upregulate pharyngeal pumping in response to food. This is a known IP3-mediated process [15]. Other IP3-mediated processes, e.g., defecation [16], were unaffected. Thus it appears that interactions between IP3Rs and myosin are required for maintaining the specificity of IP3 signalling in C. elegans and probably more generally