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ID 114610
Title Alternative
分子内結合が調節するJRABのLIMドメインによるアクチン細胞骨格の再編成
Author
Tsuchiya, Yuko The National Institute of Advanced Industrial Science and Technology|National Institutes of Biomedical Innovation, Health and Nutrition
Tomida, Yoko Tokushima University
Imoto, Issei Aichi Cancer Center Research Institute|Nagoya University KAKEN Search Researchers
Watanabe, Shio Thermo Fisher Scientific
Higo, Daisuke Thermo Fisher Scientific
Mizuguchi, Kenji National Institutes of Biomedical Innovation, Health and Nutrition
Keywords
JRAB/MICAL-L2
Actin Cytoskeleton
Intramolecular interaction
LIM domain
Content Type
Thesis or Dissertation
Description
JRAB/MICAL-L2 is an effector protein of Rab13, a member of the Rab family of small GTPase. JRAB/MICAL-L2 consists of a calponin homology domain, a LIM domain, and a coiled-coil domain. JRAB/MICAL-L2 engages in intramolecular interaction between the N-terminal LIM domain and the C-terminal coiled-coil domain, and changes its conformation from closed to open under the effect of Rab13. Open-form JRAB/MICAL-L2 induces the formation of peripheral ruffles via an interaction between its calponin homology domain and filamin. Here, we report that the LIM domain, independent of the C-terminus, is also necessary for the function of open-form JRAB/MICAL-L2. In mechanistic terms, two zinc finger domains within the LIM domain bind the first and second molecules of actin at the minus end, potentially inhibiting the depolymerization of actin filaments (F-actin). The first zinc finger domain also contributes to the intramolecular interaction of JRAB/MICAL-L2. Moreover, the residues of the first zinc finger domain that are responsible for the intramolecular interaction are also involved in the association with F-actin. Together, our findings show that the function of open-form JRAB/MICAL-L2 mediated by the LIM domain is fine-tuned by the intramolecular interaction between the first zinc finger domain and the C-terminal domain.
Journal Title
Scientific Reports
ISSN
20452322
Publisher
Springer Nature
Volume
9
Start Page
12794
Published Date
2019-09-05
Remark
内容要旨・審査要旨・論文本文の公開
本論文は,著者Kazuhisa Miyakeの学位論文として提出され,学位審査・授与の対象となっている。
Rights
This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
EDB ID
DOI (Published Version)
URL ( Publisher's Version )
FullText File
language
eng
TextVersion
ETD
MEXT report number
甲第3359号
Diploma Number
甲医第1442号
Granted Date
2020-02-27
Degree Name
Doctor of Medical Science
Grantor
Tokushima University
departments
Medical Sciences
Technical Support Department
Pharmaceutical Sciences