Tight junctions negatively regulate mechanical forces applied to adherens junctions in vertebrate epithelial tissue

The reorganization of cells in response to mechanical forces converts simple epithelial sheets into complex tissues of various shapes and dimensions. Epithelial integrity is maintained throughout tissue remodeling, but the mechanisms that regulate dynamic changes in cell adhesion under tension are not well understood. In Drosophila melanogaster, planar polarized actomyosin forces direct spatially organized cell rearrangements that elongate the body axis. We show that the LIM-domain protein Ajuba is recruited to adherens junctions in a tension-dependent fashion during axis elongation. Ajuba localizes to sites of myosin accumulation at adherens junctions within seconds, and the force-sensitive localization of Ajuba requires its N-terminal domain and two of its three LIM domains. We demonstrate that Ajuba stabilizes adherens junctions in regions of high tension during axis elongation, and that Ajuba activity is required to maintain cell adhesion during cell rearrangement and epithelial closure. These results demonstrate that Ajuba plays an essential role in regulating cell adhesion in response to mechanical forces generated by epithelial morphogenesis.

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Manipulating the Patterns of Mechanical Forces That Shape Multicellular Tissues

Physiology ◽

10.1152/physiol.00018.2019 ◽

2019 ◽

Vol 34 (6) ◽

pp. 381-391 ◽

Cited By ~ 1

Author(s):

R. Marisol Herrera-Perez ◽

Karen E. Kasza

Keyword(s):

Drosophila Melanogaster ◽

Embryonic Development ◽

Experimental Studies ◽

Model Organism ◽

Temporal Patterns ◽

Epithelial Tissue ◽

Mechanical Forces ◽

Spatial And Temporal Patterns ◽

Functional Tissue ◽

Unstructured Groups

During embryonic development, spatial and temporal patterns of mechanical forces help to transform unstructured groups of cells into complex, functional tissue architectures. Here, we review emerging approaches to manipulate these patterns of forces to investigate the mechanical mechanisms that shape multicellular tissues, with a focus on recent experimental studies of epithelial tissue sheets in the embryo of the model organism Drosophila melanogaster.

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The Interaction of JRAB/MICAL-L2 with Rab8 and Rab13 Coordinates the Assembly of Tight Junctions and Adherens Junctions

Molecular Biology of the Cell ◽

10.1091/mbc.e07-06-0551 ◽

2008 ◽

Vol 19 (3) ◽

pp. 971-983 ◽

Cited By ~ 74

Author(s):

Rie Yamamura ◽

Noriyuki Nishimura ◽

Hiroyoshi Nakatsuji ◽

Seiji Arase ◽

Takuya Sasaki

Keyword(s):

Plasma Membrane ◽

Epithelial Cells ◽

Tight Junctions ◽

Binding Protein ◽

Adherens Junctions ◽

Binding Domain ◽

Endocytic Recycling ◽

E Cadherin

The assembly of tight junctions (TJs) and adherens junctions (AJs) is regulated by the transport of integral TJ and AJ proteins to and/or from the plasma membrane (PM) and it is tightly coordinated in epithelial cells. We previously reported that Rab13 and a junctional Rab13-binding protein (JRAB)/molecule interacting with CasL-like 2 (MICAL-L2) mediated the endocytic recycling of an integral TJ protein occludin and the formation of functional TJs. Here, we investigated the role of Rab13 and JRAB/MICAL-L2 in the transport of other integral TJ and AJ proteins claudin-1 and E-cadherin to the PM by using a Ca2+-switch model. Although knockdown of Rab13 specifically suppressed claudin-1 and occludin but not E-cadherin transport, knockdown of JRAB/MICAL-L2 and expression of its Rab13-binding domain (JRAB/MICAL-L2-C) inhibited claudin-1, occludin, and E-cadherin transport. We then identified Rab8 as another JRAB/MICAL-L2-C-binding protein. Knockdown of Rab8 inhibited the Rab13-independent transport of E-cadherin to the PM. Rab8 and Rab13 competed with each other for the binding to JRAB/MICAL-L2 and functionally associated with JRAB/MICAL-L2 at the perinuclear recycling/storage compartments and PM, respectively. These results suggest that the interaction of JRAB/MICAL-L2 with Rab8 and Rab13 coordinates the assembly of AJs and TJs.

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