title: Conformational plasticity of JRAB/MICAL-L2 provides "law and order" in collective cell migration.
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.
authors: Department of Biochemistry, Tokushima University, Tokushima 770-8503, Japan.
authors: Ayuko
authors: A
authors: Sakane
authors: Image Processing Research Team, RIKEN Center for Advanced Photonics, RIKEN, Wako 351-0198, Japan.
authors: Shin
authors: S
authors: Yoshizawa
authors: Image Processing Research Team, RIKEN Center for Advanced Photonics, RIKEN, Wako 351-0198, Japan.
authors: Masaomi
authors: M
authors: Nishimura
authors: National Institutes of Biomedical Innovation, Health and Nutrition, Ibaraki 567-0085, Japan.
authors: Yuko
authors: Y
authors: Tsuchiya
authors: Translational Research Center, Ehime University Hospital, Ehime 791-0295, Japan.
authors: Natsuki
authors: N
authors: Matsushita
authors: Department of Biochemistry, Tokushima University, Tokushima 770-8503, Japan.
authors: Kazuhisa
authors: K
authors: Miyake
authors: Department of Optical Imaging, Tokushima University, Tokushima 770-8503, Japan.
authors: Kazuki
authors: K
authors: Horikawa
authors: Department of Human Genetics, Graduate School of Medical Sciences, Tokushima University, Tokushima 770-8503, Japan.
authors: Issei
authors: I
authors: Imoto
authors: Institute of Biomedical Sciences, Graduate School of Pharmaceutical Sciences, Tokushima University, Tokushima 770-8503, Japan.
authors: Chiharu
authors: C
authors: Mizuguchi
authors: Institute of Biomedical Sciences, Graduate School of Pharmaceutical Sciences, Tokushima University, Tokushima 770-8503, Japan.
authors: Hiroyuki
authors: H
authors: Saito
authors: Transdisciplinary Life Science Course, Faculty of Advanced Life Science, Hokkaido University, Sapporo 770-8503, Japan.
authors: Takato
authors: T
authors: Ueno
authors: Translational Research Center, Ehime University Hospital, Ehime 791-0295, Japan.
authors: Sachi
authors: S
authors: Matsushita
authors: Transdisciplinary Life Science Course, Faculty of Advanced Life Science, Hokkaido University, Sapporo 770-8503, Japan.
authors: Hisashi
authors: H
authors: Haga
authors: Laboratory for Mechanobiology and Bioengineering, Graduate School of Engineering, Nagoya Institute of Technology, Nagoya 466-8555, Japan.
authors: Shinji
authors: S
authors: Deguchi
authors: National Institutes of Biomedical Innovation, Health and Nutrition, Ibaraki 567-0085, Japan.
authors: Kenji
authors: K
authors: Mizuguchi
authors: Image Processing Research Team, RIKEN Center for Advanced Photonics, RIKEN, Wako 351-0198, Japan.
authors: Hideo
authors: H
authors: Yokota
authors: Department of Biochemistry, Tokushima University, Tokushima 770-8503, Japan sasaki@tokushima-u.ac.jp.
authors: Takuya
authors: T
authors: Sasaki
mesh_terms: D000185:Actinin / Q000378:metabolism; D000818:Animals; D002465:Cell Movement / Q000502:physiology; D019295:Computational Biology; D004285:Dogs; D004847:Epithelial Cells / Q000378:metabolism; D022001:Focal Adhesions / Q000378:metabolism / Q000502:physiology; D057809:HEK293 Cells; D006801:Humans; D061985:Madin Darby Canine Kidney Cells; D008840:Microfilament Proteins / Q000378:metabolism* / Q000502:physiology*; D061848:Optical Imaging; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D019108:Tight Junctions / Q000378:metabolism; D020691:rab GTP-Binding Proteins / Q000378:metabolism
chemical_list: C528177:MICALL2 protein, human; D008840:Microfilament Proteins; D000185:Actinin; C085485:RAB13 protein, human; D020691:rab GTP-Binding Proteins