Insulin-like signaling and the neural circuit for integrative behavior in C. elegans

  1. Eiji Kodama1,
  2. Atsushi Kuhara1,
  3. Akiko Mohri-Shiomi1,4,
  4. Koutarou D. Kimura1,5,
  5. Masatoshi Okumura1,
  6. Masahiro Tomioka2,
  7. Yuichi Iino2, and
  8. Ikue Mori1,3,6
  1. 1Division of Biological Science, Graduate School of Science, Nagoya University, Nagoya 464-8602, Japan;
  2. 2Molecular Genetics Research Laboratory, The University of Tokyo, Tokyo 113-0033, Japan;
  3. 3Institute for Advanced Research, Nagoya University, Nagoya 464-8602, Japan

    Abstract

    Caenorhabditis elegans exhibits a food-associated behavior that is modulated by the past cultivation temperature. Mutations in INS-1, the homolog of human insulin, caused the defect in this integrative behavior. Mutations in DAF-2/insulin receptor and AGE-1/phosphatidylinositol 3 (PI-3)-kinase partially suppressed the defect of ins-1 mutants, and a mutation in DAF-16, a forkhead-type transcriptional factor, caused a weak defect. In addition, mutations in the secretory protein HEN-1 showed synergistic effects with INS-1. Expression of AGE-1 in any of the three interneurons, AIY, AIZ, or RIA, rescued the defect characteristic of age-1 mutants. Calcium imaging revealed that starvation induced INS-1-mediated down-regulation of AIZ activity. Our results suggest that INS-1, in cooperation with HEN-1, antagonizes the DAF-2 insulin-like signaling pathway to modulate interneuron activity required for food-associated integrative behavior.

    Keywords

    Footnotes

    • 4 Present addresses: University of Texas Health Science Center at Houston, Department of Microbiology and Molecular Genetics, Houston, TX 77030, USA;

    • 5 Structural Biology Center, National Institute of Genetics, Mishima 411-8540, Japan.

    • 6 Corresponding author.

      6 E-MAIL m46920a{at}nucc.cc.nagoya-u.ac.jp; FAX 81-52-789-4558.

    • Supplemental material is available at http://www.genesdev.org.

    • Article is online at http://www.genesdev.org/cgi/doi/10.1101/gad.1479906.

      • Received August 9, 2006.
      • Accepted September 18, 2006.
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