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The enteric muscle contraction (EMC) is the last step of the defecation behavior which occurs every 50s in Caenorhabditis elegans. This EMC is regulated by intestinal and anal depressor muscles, which are innervated by GABA motor neurons. Our data show that calcineurin (tax-6) is expressed in intestinal muscle and anal depressor muscle, and the gain-of-function mutant of calcineurin, tax-6(jh107), shows defects in enteric muscle contractions. In addition, the intracellular region of EXP-1, an excitatory GABA receptor, specifically binds to calcineurin A. This interaction between TAX-6 and EXP-1 appears to be independent of both calcium and CNB, which is the calcium-binding regulatory subunit. Genetic evidence of epistasis between cnb-1(jh103) and exp-1(sa6) suggests that calcineurin functions as a negative regulator of excitatory GABA receptor in GABA signaling in C.elegans. [Copyright &y& Elsevier]

Ca2+/calmodulin-dependent calcineurin has been shown to have important roles in various Ca2+ signaling pathways. We have previously reported that cnb-1(jh103) mutants, null mutants of a regulatory B subunit, displayed pleiotropic defects including uncoordinated movement and delayed egg laying in Caenorhabditis elegans. Interestingly, gain-of-function mutants of a catalytic A subunit showed exactly opposite phenotypes to those of cnb-1(null) mutants providing an excellent genetic model to define calcium-mediated signaling pathway at the organism level. Furthermore, calcineurin is also important for normal cuticle formation, which is required for maintenance of normal body size in C.elegans. Genetic interactions between tax-6 and several mutants including egl-30 and egl-10, which are known to be involved in G-protein signaling pathways suggest that calcineurin indeed regulates locomotion and serotonin-mediated egg laying through goa-1(Goα) and egl-30(Gqα). Our results indicate that, along with CaMKII, calcineurin regulates G-protein-coupled phosphorylation signaling pathways in C.elegans. [Copyright &y& Elsevier]