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2019 Fiscal Year Final Research Report

Functional analyses of small GTPase Rab proteins and their novel guanine nucleotide exchange factors

Research Project

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Project/Area Number 17H03669
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Cell biology
Research InstitutionGunma University

Principal Investigator

Sato Ken  群馬大学, 生体調節研究所, 教授 (30311343)

Project Period (FY) 2017-04-01 – 2020-03-31
Keywords低分子量GTPase / GDP/GTP交換因子 / エンドサイトーシス
Outline of Final Research Achievements

Rab11, which is a small GTPase, is localized in the Golgi apparatus and endosomes, and plays important roles such as endocytic recycling of cell membrane proteins and cell migration. Rab11 is also suggested to be associated with serious diseases such as ovarian cancer and breast cancer. In this study, we first clarified the molecular mechanism by which the Rab11 GDP / GTP exchange factor, REI-1 / SH3BP5 family, activates Rab11 by crystal structure analysis. In addition, we performed functional analysis of SH3BP5 and SH3BP5L in cultured mammalian cells and found that they localized to recycling endosomes and regulate cell migration by controlling intracellular trafficking of integrins.

Free Research Field

細胞生物学

Academic Significance and Societal Importance of the Research Achievements

本研究によって,既知のRab GDP/GTP交換因子とは異なるアミノ酸配列を持つREI-1/SH3BP5ファミリータンパク質がどのようにしてRab11を活性化するのか明らかとなった.この発見は60種以上存在するRabタンパク質の活性化機構に新たな知見を与えるものであり、学術的意義が高いと言える。また,これらの因子がRab11の活性化を通じてガン細胞等の細胞移動を制御していることが明らかとなった.Rab11は生物にとって必須であり阻害することは困難であるが,REI-1/SH3BP5タンパク質はRab11が関連するガン等の治療薬開発の新たな標的分子となる可能性があり、社会的にも意義があると言える.

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Published: 2021-02-19  

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