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In vivo imaging of receptor trafficking of RET in organogenesis and pathogenesis

Research Project

Project/Area Number 15K21147
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field General physiology
Experimental pathology
Research InstitutionKobe University

Principal Investigator

Ito Keisuke  神戸大学, 医学研究科, 助教 (10575468)

Project Period (FY) 2015-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
KeywordsRET / GDNF / Rab11 / Dynein / 細胞外基質 / Integrin / 変異型RET / 腸管神経系 / 細胞内輸送 / CRISPR/Cas9 / β1-integrin / 末梢神経系
Outline of Final Research Achievements

Appropriate intracellular receptor trafficking underlie normal physiological activities of cells. RET, a Glial cell line neurotrophic factor receptor plays various roles in organogenesis, but its intracellular trafficking is largely unknown. In this project, I generated a knockin mouse line that express RET-GFP fusion proteins, and analyzed intracellular trafficking of RET in living cells. I found that RET exhibited polarized trafficking pattern and this pattern largely depends on types of extracellular matrices. I also found that Rab11 and Dynein pathways regulate RET trafficking. Finally, a mutant RET that can induces multiple human diseases showed aberrant localization. Therefore, it is suggested that appropriate RET trafficking is essential for normal physiological activities, and disruption of localization pattern of mutant RET leads to pathogenesis.

Report

(3 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • Research Products

    (3 results)

All 2016 2015

All Journal Article (1 results) (of which Peer Reviewed: 1 results,  Acknowledgement Compliant: 1 results) Presentation (2 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] Retrograde transport of neurotrophic factor signaling: implications in neuronal development and pathogenesis.2016

    • Author(s)
      Keisuke Ito and Hideki Enomoto
    • Journal Title

      The Journal of Biochemistry

      Volume: 160 Issue: 2 Pages: 77-85

    • DOI

      10.1093/jb/mvw037

    • NAID

      40020914022

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Presentation] Polarized intracellular trafficking of RET tyrosine kinase in living neurons2015

    • Author(s)
      Keisuke Ito, Hideki Enomoto
    • Organizer
      第38回日本神経科学大会
    • Place of Presentation
      神戸
    • Year and Date
      2015-07-28
    • Related Report
      2015 Research-status Report
  • [Presentation] Polarized trafficking of RET tyrosine kinase in migrating enteric-neural crestderived cells2015

    • Author(s)
      Keisuke Ito, Hideki Enomoto
    • Organizer
      4th International Symposium on "Development of the enteric nervous system:Cells,Singnals,Genes and Therapy"
    • Place of Presentation
      オランダ
    • Year and Date
      2015-04-19
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research

URL: 

Published: 2015-04-16   Modified: 2018-03-22  

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