C. elegans UNC-43, the type II Ca 2+ and calmodulin-dependent protein kinase (CaMKII), acts upstream of the NSY-1 MAPKKK-SEK-1 MAPKK-MAPK pathway to establish asymmetric cell fate decision in olfactory AWC neuron (Sagasti et al ., 2001; Tanaka-Hino et al ., 2002). UNC-43 also regulates several other neuronal functions including locomotion. In fact, the
unc-43(gf) gain-of-function causes severe Unc phenotype. Although the GOA-1/EGL-30 heterotrimeric G protein network is involved in UNC-43-mediated regulation of locomotion, other components acting downstream of UNC-43 in the pathway are still unknown. We have determined whether the SEK-1 MAPKK is also involved in the UNC-43 locomotory function. In contrast to
unc-43(gf) single mutants,
unc-43(gf);
sek-1(lf) double mutant animals exhibited almostly normal movement pattern. Thus, the
sek-1 loss-of-function mutation can suppress the movement defect of
unc-43(gf). Next, we examined the effect of the activated
sek-1 mutation (
sek-1-STDD ; Tanaka-Hino et al ., 2002) on the locomotion. When
sek-1-STDD was expressed by the
jkk-1 promoter (Kawasaki et al ., 1999) in N2 wild-type animals, they showed severe Unc phenotype similar to
unc-43(gf) . This Unc phenotype was suppressed by the
goa-1(lf) mutation. These results suggest that SEK-1 functions downstream of UNC-43 and upstream of GOA-1 to regulate proper movement. Kawasaki M., Hisamoto N., Iino Y., Yamamoto M., Ninomiya-Tsuji, J., Matsumoto, K. A Caenorhabditis elegans JNK signal transduction pathway regulates coordinated movement via type-D GABAergic motor neurons. EMBO J., 18: 3604-3615 (1999). Sagasti, A., Hisamoto, N., Hyodo, J., Tanaka-Hino, M., Matsumoto, K., Bargmann, C. I. The CaMKII UNC43 activates the MAPKKK NSY-1 to execute a lateral signaling decision required for asymmetric olfactory neuron fates. Cell, 105: 221-232 (2001). Tanaka-Hino, M., Sagasti, A., Hisamoto, N., Kawasaki, M., Nakano, S., Ninomiya-Tsuji, J., Bargamnn, C. I., Matsumoto, K. SEK-1 MAPKK mediates Ca 2+ signaling to determine neuronal asymmetric development in C. elegans . EMBO Rep., 3: 56-62 (2002).