RT Journal Article
SR Electronic
T1 Apical Actin-myosin Network Regulates the Tight Junction of Polarized Madin-Darby Canine Kidney Cells
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.05.30.446323
DO 10.1101/2021.05.30.446323
A1 Chia-hsuan Lu
A1 Fu-Lai Wen
A1 Shawn Ching-Chung Hsueh
A1 Wen-hsiu Wu
A1 Yu-Fang Lin
A1 Mathieu Prouveur
A1 Thomas Boudier
A1 Keng-hui Lin
YR 2021
UL http://biorxiv.org/content/early/2021/05/30/2021.05.30.446323.abstract
AB The tight junction outlines the apicolateral border of epithelial cells like a belt, sealing the paracellular space when cells form contacts with each other. The permeability and morphology of tight junction are regulated by actomyosin contractility, which has been conventionally thought from the purse-string-like circumferential actomyosin belt along tight junction. Spatially, the tight junction is close to the apical actin network, which exerts inward contractions orthogonal to the tight junction. To test the contributions from apical actin network, we laser-ablated spots on the apical surface of polarized Madin-Darby Canine Kidney (MDCK) epithelial cells. Laser ablation severed the apical cytoskeleton network, decreased in-plane tension, increased the apical surface area, and rendered the tight junction less tortuous in shape. Consistent with these observations, changes in MDCK cell sheet morphology due to cell proliferation, or perturbation with the ROCK inhibitor Y27632 increased the density of the apical actin network and decreased tight junction tortuosity. The morphological analysis revealed scutoids in flat MDCK cell sheets, contrary to predictions from a previous model that only considered cell-cell interactions as line tension. Additional cell-cell interactions from apical in-plane tension provides probable cause for the occurrence of scutoids on flat geometry. Taken together, our findings identify the importance of the apical actin network exerting in-plane apical tension to regulate tight-junction mechanobiology and epithelial cell shape.Significance Statement The tight junction is located at the apicolateral cell border and regulates paracellular diffusion. Adjacent to the tight junction, the actin cytoskeleton forms a dense network beneath the apical surface and an actomyosin belt that circumscribes the lateral surface of the cell. Tight junctions are connected to the actin cytoskeleton which regulates paracellular transport, but the role of tension-mediated regulation of the tight junction by various actin structures is poorly understood. Here, we provide evidence that tension on the tight junction is mediated by the apical actin network. Our results provide a reinterpretion of past reports and broaden our understanding the mechanobiology of tight junctions.Competing Interest StatementThe authors have declared no competing interest.