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

Abstract

The ability of a muscle to break down 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 Caenorhabditis 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 anteriorly-posteriorly to promote copulation behavior. Although WNT signaling and calcineurin have been implicated separately in muscle remodeling, we unexpectedly found that they participate in the same pathway. We show that WNT signaling through Gαo and PLC-β results in sustained Ca2+ release via IP3 and ryanodine receptors to activate calcineurin. These results highlight the utility of this new model in identifying additional molecules involved in muscle remodeling.