Developmental change in signal transduction regulating neurite outgrowth

• Project/Area Number: 16500244
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Neurochemistry/Neuropharmacology
• Research Institution: Yokohama City University
• Principal Investigator: TAKEI Kohtaro Yokohama City University, School of Medicine, Associate Professor, 医学部, 準教授 (40202163)
• Project Period (FY): 2004 – 2005
• Project Status: Completed (Fiscal Year 2005)
• Budget Amount: ¥3,400,000 (Direct Cost: ¥3,400,000); Fiscal Year 2005: ¥1,700,000 (Direct Cost: ¥1,700,000); Fiscal Year 2004: ¥1,700,000 (Direct Cost: ¥1,700,000)
• Keywords: Neurite outgrowth / Signal transduction / Developmental change / Calcium / Growth cone / NCS-1 / CALI

Research Abstract

The aid of this study is to clarify signal transduction mechanisms regulating neurite outgrowth which show dynamic change in accordance with developmental process. Calcium acts important second messenger in the intracellular signal pathways in a variety of cell function. Intracellular calcium ion is strictly regulated and its optimal concentration is required for a proper neurite outgrowth. We first examined source of calcium for neurite outgrowth and calcium-dependent signaling in cultured dorsal root ganglion (DRG) neurons from early or late stages of chick embryos. In early developmental stages, calcium release from internal stores through inositol 1.4.5-trisphosphate (IP3) receptors was found to contribute on neurite outgrowth of chick DRG neuron, while calcium increases by influxes through plasma membrane and by release form internal stores through ryanodine receptors were found to be important for the neurite outgrowth. We next examined the calcium signal cascade regulating neuri te outgrowth in the early developmental stage. Neuronal calcium sensor-1 (NCS-1) is a high-affinity and low-capacity calcium binding protein that is specifically expressed in the nervous system. We found the clustering of NCS-1 in the growth cone that is located at a distal tip of neurite in chick DRG neurons. Immunocytochemistry revealed that NCS-1 was co-localized with type 1 IP3 receptor in the growth cone. Pharmacological inhibition of IP3 receptors decreased clustering distribution of NCS-1 in the growth cones and inhibited neurite outgrowth, but not affect growth cone morphology. Acute localized loss of NCS-1 function in the growth cone induced by chromophore-assisted laser inactivation (CALI) resulted in growth arrest of neurites and lamellipodial retraction, but not filopodial retraction. These findings suggest that calcium signaling mediated by NCS-1 in growth cone may regulate the intracellular calcium signaling regulating both of growth cone morphology and neurite outgrowth, and may functionally linked to InsP_3R1 in growth cone may promote neurite outgrowth in the earty developmental stages.

Research Products

• [Journal Article] Regulation of dendritic branching and spine maturation by Semaphorin3A-Fyn Signaling (2006)
  • Author(s): Morita, A., Yamashita, N., Sasaki, Y., Uchida, Y., Nakajima, O., Nakamura, F., Yagi, T., Taniguchi, M., Usui, H., Katoh-Semba, R., Takei, K., Goshima, Y.
  • Journal Title: Journal of Neuroscience 26 Pages: 2971-2980
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Regulation of dendritic branching and spine maturation by Semaphorin3A-Fyn Signaling. (2006)
  • Author(s): Morita, A., Yamashita, N., Sasaki, Y., Uchida, Y, Nakajima, O., Nakamura, F, Yagi, T., Taniguchi, M., Usui, H., Katoh-Semba, R., Takei, K., Goshima, Y.
  • Journal Title: Journal of Neuroscience 26 Pages: 2971-2980
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] FKBP133 : A novel mouse FK-506 binding protein homolog alters growth cone morphology (2006)
  • Author(s): Nakajima, O., Nakamura, F., Yamashita, N., Tomita, Y., Syto, F, Okada, T., Iwamattsu, A., Kondo, E., Fujisawa, H., Takei, K., Goshima, Y.
  • Journal Title: Biochem Biophys.Res.Comm. (in press)
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Cdk5 and GSKβ sequentiaaly phosphorylate CRMP2 in Semaphorin-3A signaling : Implication of common phosphorylating mechanism underlyin axon guidance and Alzheimer disease (2005)
  • Author(s): Uchida, Y., Ohshima, T., Sasaki, Y., Suzuki, H., Yanai, S., Yamashita, N., Nakamura, F., Takei, K., Ihara, Y., Mikoshiba, K., Kolattukudy, P., Honnorat, J., Goshima, Y.
  • Journal Title: Genes to Cells 10 Pages: 165-179
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Cdk5 and GSKβ sequentially phosphorylate CRMP2 in Semaphorin-3A signaling : Implication of common phosphorylating mechanism underlying axon guidance and Alzheimer disease (2005)
  • Author(s): Uchida, Y., Ohshima, T., Sasaki, Y., Suzuki, H., Yanai, S., Yamashita, N., Nakamura, F., Takei, K., Ihara, Y., Mikoshiba, K., Kolattukudy, P., Honnorat, J., Goshima, Y.
  • Journal Title: Genes to Cells 10 Pages: 165-179
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Correlation between Sema3A-induced facilitation of axonal transport an local activation of a translation initiation factor eIF-4E (2004)
  • Author(s): Li, C., Sasaki, Y., Takei, K., Yamamoto, H., Shouji, M., Sugiyama, Y., Kawakami, T., Nakamura, F., Yagi, T., Ohshima, T., Goshima, Y.
  • Journal Title: Journal of Neuroscience 24 Pages: 6161-6170
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Correlation between Sema3A-induced facilitation of axonal transport and local activation of a translation initiation factor eIF-4E (2004)
  • Author(s): Li, C., Sasaki, Y., Takei, K., Yamamoto.H., Shouji, M., Sugiyama, Y, Kawakami, T., Nakamura, F., Yagi, T., Ohshima, T., Goshima, Y.
  • Journal Title: Journal of Neuroscience 24 Pages: 6161-6170
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] FKBP133 : A novel mouse FK-506 binding protein homolog alters growth conmorphology
  • Author(s): Nakajima, O., Nakamura, F., Yamashita, N., Tomita, Y., Syto, F., Okada, T., Iwamattsu, A., Kondo, E., Fujisawa, H., Takei, K., Goshima, Y.
  • Journal Title: Biochem. Biophys. Res. Comm. (印刷中)
  • Description: 「研究成果報告書概要(和文)」より