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

Abstract

Epithelia are layers of polarised cells tightly bound to each other by adhesive contacts. Epithelia act as barriers between an organism and its external environment. Understanding how epithelia maintain their essential integrity while remaining sufficiently plastic to allow events such as cytokinesis to take place is a key biological problem. In vertebrates, the remodelling and reinforcement of adherens junctions maintains epithelial integrity during cytokinesis. The involvement of tight junctions in cell division, however, has remained unexplored. Here, we examine the role of tight junctions during cytokinesis in the epithelium of the embryo. Depletion of the tight junction-associated proteins ZO-1 and GEF-H1 leads to altered cytokinesis duration and contractile ring geometry. Using a tension biosensor, we show that cytokinesis defects originate from misregulation of tensile forces applied to adherens junctions. Our results reveal that tight junctions regulate mechanical tension applied to adherens junctions, which in turn impacts cytokinesis.This article has an associated First Person interview with the first author of the paper.

Mechanosensation of Tight Junctions Depends on ZO-1 Phase Separation and Flow

“…Such func-tion has been demonstrated for AJs, where junctional tension leads to conformational changes of a-catenin and vinculin, which again increases the actin-binding capability of these AJ components to the adjacent actomyosin cortex (Gomez et al, 2011). Although the role of TJ in regulating cell-cell coupling strength remains largely unknown, recent studies showing that the TJ component ZO-1 modulates tension at cell-cell junctions (Hatte et al, 2018;Tornavaca et al, 2015) and can be stretched by tension (Spadaro et al, 2017) suggest that ZO proteins are involved in force transduction and reception at cell-cell contacts (Hashimoto et al, 2019). Our observation that TJs appear to be the predominant junction type at the EVL-YSL boundary and that there is force transduction from the actomyosin band within the YSL to the leading edge of the EVL (Behrndt et al, 2012) point to the possibility that TJ have a force-transducing function.…”

Rho Flares Repair Local Tight Junction Leaks

“…Many have speculated that tissue integrity and epithelial barrier function are challenged by naturally occurring changes in tensile force, whether due to cytokinesis, development, or (legend continued on next page) normal organ function (Arnold et al, 2017;Charras and Yap, 2018;Hatte et al, 2018). However, direct evidence that barrier function suffers because of these activities has been lacking.…”

“…In a previous study, we examined epithelial barrier function during cytokinesis by directly imaging fluorescein applied to the apical surface of a Xenopus laevis embryo as a fluorescent tracer (Higashi et al, 2016). We saw no penetrance of the tracer beyond the tight junctions, even at the contractile ring, a site that undergoes a major change in cell shape and represents a potential challenge to junction integrity (Hatte et al, 2018). However, we reasoned that small volumes of the tracer might be difficult to detect against the high background of apical fluorescein.…”

“…We next applied ZnUMBA to the unperturbed epithelium of gastrula-stage X. laevis embryos (Nieuwkoop and Faber stage 10.5-12;Nieuwkoop, 1994). At this stage of X. laevis development, epithelial tissue faces challenges to barrier function from cell division (Hatte et al, 2018;Higashi et al, 2016), pulses of contraction induced by calcium transients (Wallingford et al, 2001), and spreading of the epithelial tissue due to gastrulation (Webb and Miller, 2006). We observed sporadic, short-lived local increases in FZ3 signal at cell-cell junctions throughout the animal cap epithelium of the embryo ( Figure 1C; Video S1), suggesting that the tight junction barrier is sporadically breached then quickly repaired, consistent with the dynamic strand hypothesis of the leak pathway.…”

Atypical septate junctions maintain the somatic enclosure around maturing spermatids and prevent premature sperm release inDrosophilatestis

“…In mice testis, knockdown of claudin-11 led to sloughing off the Sertoli cells from the seminiferous tubule, indicating that the TJs are required to maintain structural integrity in an epithelium (Mazaud-Guittot et al, 2010). Recently, it has been seen in Xenopus embryos that loss of TJ proteins leads to an increase in tension on Adherens junctions during cytokinesis (Hatte et al, 2018). Therefore, apart from serving the barrier properties, SJs and TJs may also help in generating tissue resistance to mechanical strain which is essential for maintain organ shape and integrity during development and in adult stages.…”