In a reverse genetic approach to understand how body size is regulated in C. elegans we have generated a deletion allele,
sv31, of a homologue of the ribosomal protein S6 kinase (Y47D3A.16). In other organisms S6K is thought to act as a sensor of the nutritional status of the cell, and to mediate response to certain growth factors. The protein is thought to act by regulating the efficiency of translation in response to these factors. In Drosophila, mutations in S6K cause a reduction in cell and body size, a phenotype that mimics that of flies raised under nutrient-limiting conditions. Mice knockouts of this gene also result in a small phenotype. Overexpression of S6K increases cell size. Consistent with the results from these other systems,
sv31 homozygotes grow more slowly than wild type, have a reduced brood size, and grow to a final size that is slightly less than that to which wild-type worms grow. Interestingly
sv31 mutant worms also have a darker appearance, which is due to the increased size and number of fat droplets in the intestine. This suggests that these worms have a metabolic defect resulting in increased fat accumulation. A starved adult worm is smaller than normal but has decreased fat accumulation implying that
sv31 mutants do not completely phenocopy starved worms. Mutations in the insulin-signaling pathway, activated by DAF-2, as well as mutations in the TGF- pathway, activated by DAF-7, also result in increased fat accumulation. We have found strong genetic interactions with the TGF- homologue
daf-7:
sv31 strongly enhances the Daf-c phenotype of
daf-7(
e1372ts) at the semipermissive temperature.
sv31 enhances the fat accumulation seen in
daf-2(
e1370ts) at the semipermissive temperature but does not enhance the Daf-c defect.
sv31 mutant worms also have a weak bordering behavior as do certain daf mutants. CeS6K is expressed in various tissues including the intestine, hypodermis, VNC, excretory cell, muscles and in neurons both in the head and tail. CeS6K could thus function as a sensor in these cells to control behavior, growth and metabolism according to signals from the surrounding environment. We are presently conducting more experiments to characterize the role of CeS6K in C. elegans further.