Study for the mechanisms of intercellular signaling of glial cells in the central nervous system

• Project/Area Number: 15K14344
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Neurochemistry/Neuropharmacology
• Research Institution: Gunma University
• Principal Investigator: Shirao Tomoaki 群馬大学, 大学院医学系研究科, 教授 (20171043)
• Co-Investigator(Renkei-kenkyūsha): ISHIZUKA Yuta 群馬大学, 大学院・医学系研究科・神経薬理学, 助教 (50614179)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: ドレブリン / コネキシン / アクチン / GAP結合 / GAP 結合 / アストロサイト

Outline of Final Research Achievements

GAP junction plays a pivotal role for intercellular signaling of glial cells in the central nervous system. The present study indicates that drebrin binds to connexin 43 via actin-binding region 2. This suggests that the drebrin-mediated change of GAP junction function is due to the alteration of molecular interaction between drebrin, connexin43 and actin filaments. Additionally, it is indicated that the phosphorylation of drebrin at Ser 142 does not affect the binding affinity of drebrin to connexin 43 both phospho- and dephospho-mimic mutants of drebrin could bind to connexin 43.

Research Products

• [Int'l Joint Research] University of Luebeck(Germany)
• [Int'l Joint Research] University of Bergen(Norway)
• [Int'l Joint Research] University of Luebeck(Germany)
• [Journal Article] The role of drebrinin neurons (2017)
  • Author(s): Shirao T, Hanamura K, Koganezawa N, Ishizuka Y, Yamazaki H, Sekino Y.
  • Journal Title: J. Neurochem. Volume: - Issue: 6 Pages: 819-834
  • DOI: 10.1111/jnc.13988
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] The role of drebrin in dendritic spines (2017)
  • Author(s): Koganezawa N, Hanamura K, Sekino Y, Shirao T
  • Journal Title: Mol. Cell. Neurosci. Volume: - Pages: 85-92
  • DOI: 10.1016/j.mcn.2017.01.004
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Drebrin restricts rotavirus entry by inhibiting dynamin-mediated endocytosis (2017)
  • Author(s): Li B, Ding S, Feng N, Mooney N, Ooi YS, Renf L, Diep J, Kelly MR, Yasukawa LL, Patton JT, Yamazaki H, Shirao T, Jackson PK, Greenberg HB
  • Journal Title: Proc Natl Acad Sci U S A, Volume: - Issue: 18
  • DOI: 10.1073/pnas.1619266114
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] X Irradiation Induces Acute Cognitive Decline via Transient Synaptic Dysfunction. (2016)
  • Author(s): Puspitasari A, Koganezawa N, Ishizuka Y, Kojima N, Tanaka N, Nakano T, Shirao T.
  • Journal Title: Radiat Research Volume: 185 Issue: 4 Pages: 423-430
  • DOI: 10.1667/rr14236.1
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Allopregnanolone increases mature excitatory synapses along dendrites via protein kinase A signaling (2015)
  • Author(s): Shimizu H, Ishizuka Y, Yamazaki H, Shirao T.
  • Journal Title: Neuroscience Volume: 305 Pages: 139-145
  • DOI: 10.1016/j.neuroscience.2016.03.015
  • Peer Reviewed
• [Journal Article] A novel role for drebrin in regulating progranulin bioactivity in bladder cancer (2015)
  • Author(s): Xu SQ, Buraschi S, Morcavallo A, Genua M, Shirao T, Peiper SC, Gomella LG, Birbe R, Belfiore A, Iozzo RV, Morrione A.
  • Journal Title: Oncotarget Volume: 6 Issue: 13 Pages: 10825-10839
  • DOI: 10.18632/oncotarget.3424
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Nuclear translocation of calcium/calmodulin-dependent protein kinase IIδ3 promoted by protein phosphatase-1 enhances brain-derived neurotrophic factor expression in dopaminergic neurons (2015)
  • Author(s): Shioda N, Sawai M, Ishizuka Y, Shirao T., Fukunaga K
  • Journal Title: J. Biol. Chem. Volume: 290 Issue: 35 Pages: 21663-21675
  • DOI: 10.1074/jbc.m115.664920
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Early-stage development of human induced pluripotent stem cell-derived neurons. (2015)
  • Author(s): Ohara Y, Koganezawa N, Yamazaki H, Roppongi RT, Sato K, Sekino Y, Shirao T.
  • Journal Title: J Neurosci Res. Volume: 93 Issue: 12 Pages: 1804-1813
  • DOI: 10.1002/jnr.23666
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] Study for Interaction between Drebrin and Connexin 43 in Glial assembly (2016)
  • Author(s): 石塚佑太、Justus Ernesti, 松本 瑛未, 山﨑 博幸, 白尾 智明
  • Organizer: 第38回日本生物学的精神医学会・第59回日本神経化学会大会 合同年会
  • Place of Presentation: 福岡国際会議場（福岡・博多）
  • Year and Date: 2016-09-08
• [Presentation] Novel actin-dependent mechanism of synaptic plasticity (2015)
  • Author(s): Shirao T
  • Organizer: Manitoba Neuroscience Network (MNS) Seminar
  • Place of Presentation: Winipeg, Canada
  • Year and Date: 2015-10-13
  • Invited
• [Presentation] Deletion of drebrin A impairs hippocampal synaptic plasticity and hippocampus-dependent fear learning in adulthood (2015)
  • Author(s): Yasuda H., Kojima N., Hanamura K., Shirao T
  • Organizer: 第58回日本神経化学大会
  • Place of Presentation: 大宮ソニックシティ（埼玉県さいたま市）
  • Year and Date: 2015-09-11
• [Presentation] Drebrin knockout results in the impairment of olfaction and adult neurogenesis (2015)
  • Author(s): Kajita Y, Shirao T
  • Organizer: 25th ISN Biennial Meeting
  • Place of Presentation: Cairns, Australia
  • Year and Date: 2015-08-23
  • Int'l Joint Research
• [Remarks] 群馬大学大学院医学系研究科神経薬理学分野
  • URL: http://neuro.dept.med.gunma-u.ac.jp/
• [Remarks] 群馬大学大学院医学系研究科 神経薬理学
  • URL: http://neuro.dept.med.gunma-u.ac.jp/