Functional analysis of SHP-1 in the central nervous systems

• Project/Area Number: 26830028
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Nerve anatomy/Neuropathology
• Research Institution: Osaka University
• Principal Investigator: Fujita Yuki 大阪大学, 医学(系)研究科(研究院), 助教 (60631215)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 中枢神経 / SHP-1

Outline of Final Research Achievements

Protein tyrosine phosphatases regulate various signaling mechanisms in the central nervous system (CNS). Src homology 2-containing phosphatase (SHP)-1 is the classical non-receptor protein tyrosine phosphatase (PTP), and involved in axon growth inhibition and neuronal apoptosis. The longer isoform of SHP-1, SHP-1L has also been identified but its role in the CNS remains to be unclear. In this study, we show that overexpression of SHP-1L as well as SHP-1 increases neuronal apoptosis. However, overexpression of SHP-1 or SHP-1L in mouse cortical neurons does not affect neurite length. Filamin A (FLNa), which is an actin-binding cytoskeletal protein, inhibits apoptosis induced by SHP-1 and SHP-1L. Co-expression of SHP-1 along with FLNa increases cytoplasmic localization of SHP-1. Our results suggest that SHP-1 and SHP-1L negatively regulates neuronal survival via FLNa.

Research Products

• [Journal Article] Lrig2 negatively regulates ectodomain shedding of axon guidance receptors by ADAM proteases. (2015)
  • Author(s): van Erp, S., van den Heuvel, D.M.A., Fujita, Y., Robinson, R.A., Hellemons, A.J., Adolfs, Y., Van Battum, E.Y., Blokhuis, A.M., Kuijpers, M., Demmers, J., Hedman, H., Hoogenraad, C.C., Siebold, C., Yamashita, T. and Pasterkamp, R.J.
  • Journal Title: Dev. Cell Volume: 35 Issue: 5 Pages: 537-552
  • DOI: 10.1016/j.devcel.2015.11.008
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Acetylation of NDPK-D regulates its subcellular localization and cell survival. (2015)
  • Author(s): Fujita, Y., Fujiwara, K., Zenitani, S. and Yamashita, T.
  • Journal Title: PLoS ONE Volume: 10 Issue: 10 Pages: e0139616-e0139616
  • DOI: 10.1371/journal.pone.0139616
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] The functions and signaling pathways induced by the interactions of APP–related molecules with p75NTR. (2014)
  • Author(s): Fujita, Y., and Yamashita T.
  • Journal Title: Receptors & Clinical Investigation Volume: 1 Pages: 299-303
  • Peer Reviewed
• [Journal Article] Effect of the Sigma-1 receptor on neurite outgrowth. (2014)
  • Author(s): Kimura, Y., Fujita, Y., and Yamashita, T.
  • Journal Title: Receptors & Clinical Investigation Volume: 1 Pages: 8-12
  • Peer Reviewed
• [Journal Article] Role of DAPK in neuronal cell death. (2014)
  • Author(s): Fujita, Y. and Yamashita, T.
  • Journal Title: Apoptosis Volume: 19 Pages: 339-345
  • Peer Reviewed
• [Journal Article] Axon growth inhibition by Rho/ROCK. (2014)
  • Author(s): Fujita, Y. and Yamashita, T.
  • Journal Title: Front. Neurosci. Volume: 8 Pages: 338-338
  • Peer Reviewed
• [Remarks] 大阪大学大学院 医学系研究科 分子神経科学
  • URL: http://www.med.osaka-u.ac.jp/pub/molneu/index.html