Fig. 4.

A genetic model for regulation of polycystin signaling by cwp-5. Our studies support a model in which CWP-5 facilitates polycystin signaling by repressing latent, toxic effects of the polycystins on sensory transduction. In wild-type animals, the sensory signals that elicit response behavior in C. elegans males are transduced both by the canonical LOV-1/PKD-2 polycystin complex, as well as by a secondary, as-yet-unidentified pathway (designated ‘X’), as shown in the central line. When cwp-5 function is lost in animals lacking both polycystins, no effect is seen, indicating that cwp-5 acts in the polycystin pathway. However, the loss of cwp-5 enhances the sensory defects of single polycystin mutants; this enhancement is dependent on the function of the remaining polycystin. The simplest genetic explanation for these observations is that cwp-5 mutants reveal that each of the polycystins has a latent capacity to interfere with the secondary pathway, as indicated in the upper and lower pathways. In wild-type animals, cwp-5 is likely to prevent the manifestation of this aberrant function; in addition, cwp-5 may also directly facilitate the response-promoting activity of the polycystins (dashed line). See Discussion for details.