Cyclic GMP-dependent protein kinase EGL-4 controls body size and lifespan in C elegans.
We designed an automatic system to measure body length, diameters and volume of a C. elegans worm. By using this system, mutants with an increased body volume exceeding 50% were isolated. Four of them are grossly normal in morphology and development, grow longer to be almost twice as big, and have weak egg-laying defects and extended lifespan. All the four mutants have a mutation in the egl-4 gene. We show that the egl-4 gene encodes cGMP-dependent protein kinases. egl-4 promoter::gfp fusion genes are mainly expressed in head neurons, hypodermis, intestine and body wall muscles. Procedures to analyze morphology and volume of major organs were developed. The results indicate that volumes of intestine, hypodermis and muscle and cell volumes in intestine and muscle are increased in the egl-4 mutants, whereas cell numbers are not. Experiments on genetic interaction suggest that the cGMP-EGL-4 signaling pathway represses body size and lifespan through DBL-1/TGF-beta and insulin pathways, respectively.
Hirose
Takashi
T
Department of Biology, Faculty of Sciences, Kyushu University Graduate School, Hakozaki, Fukuoka 812-8581, Japan. yohshscb@mbox.nc.kyushu-u.ac.jp
Nakano
Yoshiya
Y
Nagamatsu
Yasuko
Y
Misumi
Takashi
T
Ohta
Hiromitsu
H
Ohshima
Yasumi
Y
D000595:Amino Acid Sequence; D000818:Animals; D001824:Body Constitution / Q000235:genetics*; D017173:Caenorhabditis elegans / Q000235:genetics / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics*; D006152:Cyclic GMP / Q000378:metabolism*; D017869:Cyclic GMP-Dependent Protein Kinases / Q000235:genetics*; D020869:Gene Expression Profiling; D049452:Green Fluorescent Proteins; D008136:Longevity / Q000235:genetics*; D008164:Luminescent Proteins / Q000235:genetics; D008969:Molecular Sequence Data; D009154:Mutation; D011993:Recombinant Fusion Proteins / Q000235:genetics
D029742:Caenorhabditis elegans Proteins; D008164:Luminescent Proteins; D011993:Recombinant Fusion Proteins; D049452:Green Fluorescent Proteins; D017869:Cyclic GMP-Dependent Protein Kinases; C470349:EGL-4 protein, C elegans; D006152:Cyclic GMP