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Mol Biol Cell. 2016 Oct 15;27(20):3095-3108. Epub 2016 Aug 31.

Conformational plasticity of JRAB/MICAL-L2 provides "law and order" in collective cell migration.

Author information

1
Department of Biochemistry, Tokushima University, Tokushima 770-8503, Japan.
2
Image Processing Research Team, RIKEN Center for Advanced Photonics, RIKEN, Wako 351-0198, Japan.
3
National Institutes of Biomedical Innovation, Health and Nutrition, Ibaraki 567-0085, Japan.
4
Translational Research Center, Ehime University Hospital, Ehime 791-0295, Japan.
5
Department of Optical Imaging, Tokushima University, Tokushima 770-8503, Japan.
6
Department of Human Genetics, Graduate School of Medical Sciences, Tokushima University, Tokushima 770-8503, Japan.
7
Institute of Biomedical Sciences, Graduate School of Pharmaceutical Sciences, Tokushima University, Tokushima 770-8503, Japan.
8
Transdisciplinary Life Science Course, Faculty of Advanced Life Science, Hokkaido University, Sapporo 770-8503, Japan.
9
Laboratory for Mechanobiology and Bioengineering, Graduate School of Engineering, Nagoya Institute of Technology, Nagoya 466-8555, Japan.
10
Department of Biochemistry, Tokushima University, Tokushima 770-8503, Japan sasaki@tokushima-u.ac.jp.

Abstract

In fundamental biological processes, cells often move in groups, a process termed collective cell migration. Collectively migrating cells are much better organized than a random assemblage of individual cells. Many molecules have been identified as factors involved in collective cell migration, and no one molecule is adequate to explain the whole picture. Here we show that JRAB/MICAL-L2, an effector protein of Rab13 GTPase, provides the "law and order" allowing myriad cells to behave as a single unit just by changing its conformation. First, we generated a structural model of JRAB/MICAL-L2 by a combination of bioinformatic and biochemical analyses and showed how JRAB/MICAL-L2 interacts with Rab13 and how its conformational change occurs. We combined cell biology, live imaging, computational biology, and biomechanics to show that impairment of conformational plasticity in JRAB/MICAL-L2 causes excessive rigidity and loss of directionality, leading to imbalance in cell group behavior. This multidisciplinary approach supports the concept that the conformational plasticity of a single molecule provides "law and order" in collective cell migration.

PMID:
27582384
PMCID:
PMC5063617
DOI:
10.1091/mbc.E16-05-0332
[Indexed for MEDLINE]
Free PMC Article

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