RT Journal Article
SR Electronic
T1 Tension-dependent stretching and folding of ZO-1 controls the localization of its interactors
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 156513
DO 10.1101/156513
A1 Domenica Spadaro
A1 Shimin Le
A1 Thierry Laroche
A1 Isabelle Mean
A1 Lionel Jond
A1 Jie Yan
A1 Sandra Citi
YR 2017
UL http://biorxiv.org/content/early/2017/06/27/156513.abstract
AB Tensile forces regulate epithelial homeostasis, but the molecular mechanisms behind this regulation are poorly understood. Using structured illumination microscopy and proximity ligation assays we show that the tight junction protein ZO-1 undergoes actomyosin tension-dependent stretching and folding in vivo. Magnetic tweezers experiments using purified ZO-1 indicate that pN-scale tensions (~2-4 pN) are sufficient to maintain the stretched conformation of ZO-1, while keeping its structured domains intact. Actomyosin tension and substrate stiffness regulate the localization and expression of the transcription factor DbpA and the tight junction membrane protein occludin in a ZO-1/ZO-2-dependent manner, resulting in modulation of gene expression, cell proliferation, barrier function and cyst morphogenesis. Interactions between the N-terminal (ZPSG) and C-terminal domains of ZO-1 prevent binding of DbpA to the ZPSG, and folding is antagonized by heterodimerization with ZO-2. We propose that tensile forces regulate epithelial homeostasis by activating ZO proteins through stretching, to modulate their protein interactions and downstream signaling.