WNT regulates programmed muscle remodeling through PLC-β and calcineurin in C. elegans males

Abstract

A muscle's ability to breakdown and reform fibers is vital for development; however if unregulated, abnormal muscle remodeling can occur, such as in the heart following cardiac infarction. To study how normal developmental remodeling is mediated, we used fluorescently tagged actin, mutant analyses, Ca2+ imaging, and controlled Ca2+ release to determine the mechanisms regulating a conspicuous muscle change that occurs in C. elegans males. In hermaphrodites and larval males, the single-cell anal depressor muscle, used for waste expulsion, contains bilateral dorsal-ventral sarcomeres. However prior to male adulthood, the muscle sex-specifically remodels its sarcomeres anterior-posteriorly to promote copulation behavior. Although WNT signaling and calcineurin have been implicated separately in muscle remodeling, unexpectedly we found that they participate in the same pathway. We show that WNT signaling through Go and PLC-β results in sustained Ca2+ release via IP(3) and ryanodine receptors to activate calcineurin. These results highlight the utility of this new model in identifying additional molecules involved in muscle remodeling.