Studies of roles of G proteins in integration of axon guidance signaling

• Project/Area Number: 15K07928
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Biological pharmacy
• Research Institution: Kyoto University
• Principal Investigator: Negishi Manabu 京都大学, 生命科学研究科, 教授 (60201696)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: Ras / Rho / G protein / 神経 / 軸索 / 樹状突起 / スパイン / ガイダンス / R-Ras / BDNF / neuron / G-protein / axon / RasGRF / TC21 / M-Ras / afadin / spine / splicing / effector

Outline of Final Research Achievements

R-Ras subfamily small GTPases have essential roles in multiple phases of developments of neurons. We have examined the roles of TC21, a member of R-Ras subfamily, and we found that TC21 was specifically expressed in spines and promoted spine maturation through afadin, a downstream effector of TC21. We also examined the upstream of R-Ras for R-Ras-mediated axon outgrowth, and we found that RasGRF1 was a GEF for R-Ras and BDNF activated R-Ras through RasGRF1, promoting axon outgrowth.

Research Products

• [Journal Article] Cystine uptake through the cystine/glutamate antiporter xCT triggers glioblastoma cell death under glucose deprivation (2017)
  • Author(s): Goji, T., Takahara, K., Negishi, M. and Katoh, H.
  • Journal Title: J. Biol. Chem. Volume: 292 Issue: 48 Pages: 19721-19732
  • DOI: 10.1074/jbc.m117.814392
  • NAID: 120006482852
  • Peer Reviewed
• [Journal Article] EphA2 is a key effector of the MEK/ERK/RSK pathway regulating glioblastoma cell proliferation (2016)
  • Author(s): Yuho Hamaoka, Manabu Negishi, Hironori Katoh
  • Journal Title: Cellular Signalling Volume: 28 Issue: 8 Pages: 937-945
  • DOI: 10.1016/j.cellsig.2016.04.009
  • NAID: 120006414205
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Tyrosine phosphorylation of SGEF regulates RhoG activity and cell migration (2016)
  • Author(s): Yusuke Okuyama, Kentaro Umeda, Manabu Negishi, Hironori Katoh
  • Journal Title: PLOS ONE Volume: 11 Issue: 7 Pages: 1-13
  • DOI: 10.1371/journal.pone.0159617
  • NAID: 120005829407
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] HGF-induced serine 897 phosphorylation of EphA2 regulates epithelial morphogenesis of MDCK cells in 3D culture (2015)
  • Author(s): Kohei Harada, Manadu Negishi, and Hironori Katoh
  • Journal Title: Journal of Cell Science Volume: 128 Issue: 10 Pages: 1912-1921
  • DOI: 10.1242/jcs.163790
  • NAID: 120006414204
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] A short splicing isoform of afadin suppresses the cortical axon branching in a dominant-negative manner (2015)
  • Author(s): Umeda K, Iwasawa N, Negishi M, Oinuma I
  • Journal Title: Molecular Biology of the Cell Volume: 26 Issue: 10 Pages: 1957-1970
  • DOI: 10.1091/mbc.e15-01-0039
  • NAID: 120005997939
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Mph/ephrin reverse signalling induces axonal retraction through RhoA/ROCK pathway (2015)
  • Author(s): Takeuchi Shingo, Hironori Katoh, and Manabu Negishi
  • Journal Title: Journal of Biochemistry Volume: 158 Issue: 3 Pages: 245-252
  • DOI: 10.1093/jb/mvv042
  • Peer Reviewed