RRC ID 45803
Author Sakane A, Yoshizawa S, Nishimura M, Tsuchiya Y, Matsushita N, Miyake K, Horikawa K, Imoto I, Mizuguchi C, Saito H, Ueno T, Matsushita S, Haga H, Deguchi S, Mizuguchi K, Yokota H, Sasaki T.
Title Conformational plasticity of JRAB/MICAL-L2 provides "law and order" in collective cell migration.
Journal Mol Biol Cell
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.
Volume 27(20)
Pages 3095-3108
Published 2016-10-15
DOI 10.1091/mbc.E16-05-0332
PII mbc.E16-05-0332
PMID 27582384
PMC PMC5063617
MeSH Actinin / metabolism Animals Cell Movement / physiology Computational Biology Dogs Epithelial Cells / metabolism Focal Adhesions / metabolism Focal Adhesions / physiology HEK293 Cells Humans Madin Darby Canine Kidney Cells Microfilament Proteins / metabolism* Microfilament Proteins / physiology* Optical Imaging Protein Binding Protein Structure, Tertiary Protein Transport Tight Junctions / metabolism rab GTP-Binding Proteins / metabolism
IF 3.791
Times Cited 9
DNA material CSII-CMV-MCS-IRES2-Bsd (RDB04385) pCMV-VSV-G-RSV-Rev (RDB04393) pCAG-HIVgp (RDB04394).