unc-43 is the only known gene that encodes the CaMKII in C. elegans. Studies from other labs have shown that UNC-43 regulates diverse behaviors in C. elegans, including locomotion, egg-laying, and defecation (Reiner et al., 1999). Our previous work has demonstrated that a loss-of-function (lf) mutation in
unc-43 causes a reduction in the expression of
tph-1, which encodes the serotonin synthesis enzyme tryptophan hydroxylase, in the ADF neurons, but that
tph-1 expression in other serotonergic neurons is unaffected. In addition, an
unc-43 gain-of-function (gf) mutation could suppress the downregulation of
tph-1 expression in the TRPV cation channel mutants,
osm-9(
yz6) and
ocr-2(
yz5) (Zhang et al., 2004). These neuron type- specific effects suggest that UNC-43, OSM-9 and OCR-2 might act in a linear signaling pathway to control
tph-1 expression in the ADF neurons. To study the functions and role of UNC-43 in the ADF neurons, we generated an
unc-43 construct under the control of the Ptph-1(BC) promoter element that is expressed only in the ADF neurons. Since CaMKII mediates calcium signaling, UNC-43 might be activated by OSM-9/OCR-2 channel-induced calcium signaling and upregulates
tph-1 expression. We are currently determining the subcellular localization of UNC-43 in the ADF neuron in
ocr-2 and
osm-9 mutants, and test whether UNC-43 directly interacts with the OCR-2/OSM-9 channel. Our goal is to study the signaling pathway from the OCR-2/OSM-9 channel to transcriptional regulation of the
tph-1 gene and to understand how
unc-43 is involved in this pathway in the ADF neurons. ReferenceReiner, D.J., Newton, E.M., Tian, H., and Thomas, J.H. (1999). Diverse behavioural defects caused by mutations in Caenorhabditis elegans
unc-43 CaM Kinase II. Nature 402, 199-203.Zhang, S., Sokolchik, I., Blanco, G., Sze, J.Y. (2004). Caenorhabditis elegans TRPV ion channel regulates 5HT biosynthesis in chemosensory neurons. Development 131,1629-1638.