FY2017 Annual Report

Principal Investigator: Ichiro Maruyama
Research Theme: Information Processing by Life

Abstract

In order to survive, animals must closely monitor environmental changes, and must keep the memory as experiences to adjust their behavior to the environment. We are interested in understanding how neuronal networks process environmental information to regulate animal behaviors, including decision-making, learning and memory. In previous years, we developed protocols to study associative learning and memory in the nematode Caenorhabditis elegans as a model organism. C. elegans is innately attracted to propanol, a short-chain alcohol, and avoids acid such as pH 4.0. After repeated conditioning C. elegans with propanol and acid, it associates the two stimuli and avoid propanol. C. elegans retains the memory up to 24 hours as long-term associative memory. In the present fiscal year, we have been trying to identify neuronal circuits responsible for the memory trace in the C. elegans nervous system by using multiple techniques including genetic rescue experiments and Ca2+ imaging analysis of neuronal activity. Optogenetics is also used to induce memories by expressing an artificial ion channel such as channelrhodopsin in specific neurons. Electrophysiology has been used to understand how electrical signals are transmitted along neurites of major gustatory sensory neurons. To understand decision-making in C. elegans, we also started analysis of its behavior on salt gradients.

We are also interested in understanding how neurons/cells detect extracellular information and transmit it into inside the cell. For the last three decades, ligand-induced dimerization has been widely thought to be a common property of transmembrane signaling by receptors for all known growth factor and cytokines, among others. In previous years, however, we found that receptors for epidermal growth factor (EGF), nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) have a preformed, yet inactive, dimeric structure prior to ligand binding. We have also found that a receptor-type guanylyl cyclase, GCY-14, exists in homodimeric form on the cell surface of a sensory neuron. Based on the results, we proposed an alternative ‘rotation model’, in which ligand binding to the extracellular domains induces a rotation of the transmembrane domains parallel to the plane of the membrane. This activates the intracellular domains, which often encode or physically interact with a kinase, by rearranging their dimeric structures. To examine the model, we are currently trying to determine three dimensional structures of the receptor dimers. We are also analyzing co-operative interaction between EGF and its receptor EGFR, which is observed only in dimers.

These results provide insights into the molecular mechanism underlying information transfer from the outside of neurons/cells to the inside, as well as an understanding of neuronal networks responsible for associative learning and memory. These findings may also be invaluable in developing pharmaceuticals for human diseases such as cancers and mental diseases.

1. Staff

  • Dingze Mang, Postdoctoral Scholar (until April 30, 2017)
  • Yuto Momohara, Postdoctoral Scholar
  • Andrew Mugo, Postdoctoral Scholar
  • Takashi Murayama, Technical Staff
  • Hitomi Ohtaki, Research Unit Administrator
  • Endang Rinawati Purba, Postdoctoral Scholar
  • Eiichiro Saita, Technical Staff
  • Vimbai Samukange, Postdoctoral Scholar

2. Graduate and other students

  • Tosif Ahamed, PhD Student
  • Dong Cao, PhD Student
  • Tsung-Yen Huang, Rotation Student (January 11, - April 30, 2017)
  • Kazuto Kawamura, PhD Student
  • Viktoras Lisicovas, PhD Student
  • Emiri Watanabe, Research Intern (August 10, - September 26, 2017)

3. Collaborations

3.1 Functional analyses of small G protein and their downstream proteins

  • Type of collaboration: Joint research
  • Researchers:
    • Ken-ichi Kariya, University of the Ryukyus
    • Tsuyoshi Asato, University of the Ryukyus
    • Kimiko Nonaka, University of the Ryukyus

3.2 Study of signal transduction pathways that regulate cellular functions

  • Type of collaboration: Joint research
  • Researchers:
    • Ken-ichi Kariya, University of the Ryukyus
    • Tsuyoshi Asato, University of the Ryukyus
    • Kimiko Nonaka, University of the Ryukyus

3.3 Social interaction and anxiety of genetically modified mice

  • Type of collaboration: Joint research
  • Researchers:
    • Ken-ichi Kariya, University of the Ryukyus
    • Tsuyoshi Asato, University of the Ryukyus
    • Kimiko Nonaka, University of the Ryukyus

3.4 Analysis of Rap2 function in skin wound healing

  • Type of collaboration: Joint research
  • Researchers:
    • Ken-ichi Kariya, University of the Ryukyus
    • Tsuyoshi Asato, University of the Ryukyus
    • Kimiko Nonaka, University of the Ryukyus

4. Publications

4.1 Journals

  1. Canu, N., Pagano, I., La Rosa, L. R., Pellegrino, M., Ciotti, M. T., Mercanti, D., Moretti, F., Sposato, V., Triaca, V., Petrella, C., Maruyama, I. N., Levi, A. and Calissano, P. (2017). Association of TrkA and APP Is Promoted by NGF and Reduced by Cell Death-Promoting Agents. Front Mol Neurosci.
  2. Endang, P. R., Saita, E.-i. and Maruyama, I. N. (2017). Activation of the EGF Receptor by Ligand Binding and Oncogenic Mutations: The “Rotation Model”. Cells. 6, 1-19.
  3. Nishijima, S. and Maruyama, I. N. (2017). Appetitive Olfactory Learning and Long-Term Associative Memory in Caenorhabditis elegans. Front. Behav. Neurosci. 11, 1-13.
  4. Murayama, T. and Maruyama, I. N. (2017). Plate Assay to Determine Caenorhabditis elegans Response to Water Soluble and Volatile Chemicals  bio-protocol. 8.

4.2 Oral and Poster Presentations

  1. Saita, E.-i., Mang, D. and Maruyama, I. N. (2017) A single EGF molecule activates a preformed EGFR dimer: a single-molecule multi-color TIRF microscopy study. 2017 ASBMB Annual Meeting. McCormick Place, Chicago, USA. (April 22-26)
  2. Maruyama, I. N. (2017) The “rotation model” for transmembrane signaling by cell surface receptors. BIT'S 7TH ANNUAL WORLD CONGRESS OF MOLECULAR & CELL BIOLOGY. Xi'an, China. (April 25-27)
  3. Kawamura, K., Murayama, T. and Maruyama, I. N. (2017) Forward Genetic Screen for Adult-Onset Motor Deficits in C. elegans. Keystone Symposia: Aging and Mechanisms of Aging-Related Disease. Yokohama, Japan. (May15-19) [Poster Presentation]
  4. Kawamura, K., Murayama, T. and Maruyama, I. N. (2017) Forward Genetic Screen for Adult-Onset Motor Deficits in C. elegans. Keystone Symposia: Aging and Mechanisms of Aging-Related Disease. Yokohama, Japan. (May15-19) [Oral Presentation]
  5. Ahamed, T. (2017) The chaotic worm: Capturing the continuous complexity of natural behavior in the movement of C. elegans. 21st International C. elegans Conference. (June21-24) [Oral Presentation]
  6. Ahamed, T. (2017) The deterministic dynamics of random search in C. elegans. 21st International C. elegans Conference. UCLA, LA, USA. (June21-24) [Poster Presentation]
  7. Momohara, Y., Shindou, T., Shindou, M., Murayama, T., Wickens, J. and Maruyama, I. N. (2017) The active signal propagation of chemosensory neurons in C. elegans. 21st International C. elegans Conference. UCLA, LA, USA. (June21-24)
  8. Murayama, T. (2017) Neural circuit basis for the behavioral switch in C. elegans chemotaxis to alkaline pH. 21st International C. elegans Conference. UCLA, LA, USA. (June21-24)
  9. Momohara, Y., Shindou, T., Shindou, M., Murayama, T., Wickens, J. and Maruyama, I. N. (2017) The active propagation of chemosensory neurons in C. elegans. The 40th Annual Meeting of Japan Neuroscience Society. Makuhari, Chiba, Japan. (July 19-22)
  10. Saita, E.-i., Mang, D. and Maruyama, I. N. (2017) A single EGF molecule is sufficient to activate a preformed EGFR dimer. The 55th Annual Meeting of The Biophysical Society of Japan. Kumamoto University, Kumamoto, Japan. (September 19-21) 
  11. Saita, E.-i. and Maruyama, I. N. (2017) Activation of preformed EGFR dimers by binding of single EGF molecules: Negative cooperativity. 62nd Annual Meeting of Biophysical Society. Moscone Center, San Francisco, CA, USA. (February 17-22)

5. Meetings and Events

5.1 Seminar

Title: Plasticity of developmental gene regulatory networks in C. elegans

  • Speaker: Joel Rothman
  • Date: July 27th 2017
  • Venue: OIST Lab1 D015

Title: The immune defense of shrimp gills revealed by Marsupenaeus japonicus gill C-type lectin (MjGCTL)

  • Speaker: Rod Russel Alenton
  • Date: August 22nd 2017
  • Venue: OIST Lab1 D014