Identification and characterization of a putative basic helix-loop-helix (bHLH) transcription factor interacting with calcineurin in C. elegans.

Calcineurin is a Ca(2+)/Calmodulin activated Ser/Thr phosphatase that is well conserved from yeast to human. It is composed of catalytic subunit A (CnA) and regulatory subunit B (CnB). C. elegans homolog of CnA and CnB has been annotated to tax-6 and cnb-1, respectively and in vivo function of both genes has been intensively studied. In C. elegans, calcineurin play roles in various signaling pathways such as fertility, movement, body size regulation and serotonin-mediated egg laying. In order to understand additional signaling pathway(s) in which calcineurin functions, we screened for binding proteins of TAX-6 and found a novel binding protein, HLH-11. The HLH-11, a member of basic helix-loop-helix (bHLH) proteins, is a putative counterpart of human AP4 transcription factor. Previously bHLH transcription factors have been implicated to regulate many developmental processes such as cell proliferation and differentiation, sex determination and myogenesis. However, the in vivo function of hlh-11 is largely unknown. Here, we show that hlh-11 is expressed in pharynx, intestine, nerve cords, anal depressor and vuvla muscles where calcineurin is also expressed. Mutant analyses reveal that hlh-11 may have role(s) in regulating body size and reproduction. More interestingly, genetic epistasis suggests that hlh-11 may function to regulate serotonin-mediated egg laying at the downstream of tax-6.