The mechanobiology of tight junctions

Abstract

Tight junctions (TJ) play a central role in the homeostasis of epithelial and endothelial tissues, by providing a semipermeable barrier to ions and solutes, by contributing to the maintenance of cell polarity, and by functioning as signaling platforms. TJ are associated with the actomyosin and microtubule cytoskeletons, and the crosstalk with the cytoskeleton is fundamental for junction biogenesis and physiology. TJ are spatially and functionally connected to adherens junctions (AJ), which are essential for the maintenance of tissue integrity. Mechano-sensing and mechano-transduction properties of several AJ proteins have been characterized during the last decade. However, little is known about how mechanical forces act on TJ and their proteins, how TJ control the mechanical properties of cells and tissues, and what are the underlying molecular mechanisms. Here I review recent studies that have advanced our understanding of the relationships between mechanical force and TJ biology.

A microtubule‐LUZP1 association around tight junction promotes epithelial cell apical constriction

“…Finally, this LUZP1‐based mechanism sheds new light on the importance of the association between TJs and CRs for vertebrate apical constriction. TJs are vertebrate‐specific junctions that are not only crucial for paracellular barriers with selective paracellular permeability, but also as signaling hubs regulating a variety of cellular events (Tsukita et al , 2001; Raleigh et al , 2011; Krug et al , 2014; Suzuki et al , 2014; Tamura & Tsukita, 2014; Saitoh et al , 2015; Tanaka et al , 2015, 2016; Zihni et al , 2016; Tanaka et al , 2017; Odenwald et al , 2018; Tanaka et al , 2018; Citi, 2019; Nakamura et al , 2019; Shigetomi & Ikenouchi, 2019; Tsukita et al , 2019b). Notably, in the context of TJ maturation, the association between actomyosin CRs and TJs is known to be important.…”

Preliminary Assessment of the Mucosal Toxicity of Tea Tree (Melaleuca alternifolia) and Rosemary (Rosmarinus officinalis) Essential Oils on Novel Porcine Uterus Models

“…Zonula occludens 1 (ZO-1), a member of the membrane-associated guanylate kinase protein family, serves as a scaffold to organize transmembrane tight junction (TJ) proteins and plays a key role in retaining barrier integrity and TJs during pathological injury [46,47]. Its distribution was examined as a marker protein for tight junctional complexes.…”

Tissue engineering of the biliary tract and modelling of cholestatic disorders

“…Bile flow and its disruption play a key role in cholestasis. Systems incorporating flow enable studies on the function of mechanosensing organelles, such as cilia, which are pivotal for the pathogenesis of ciliopathies; furthermore, physiological mechanical stimulisuch as fluid shear stressinduce strengthening of cadherin-based cell junctions that promote the formation of tight junctions, 109,110 resulting in enhanced cell polarisation and increased epithelial barrier function. 111 However, both multicellular organoids and 3D printing generate bioengineered tissue which is maintained in static culture.…”