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The mechanobiology of tight junctions

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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.

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Abbreviations

ABR:

actin binding region

AFM:

atomic force microscopy

AJ:

adherens junction

CAM:

cell adhesion molecule

CAR:

Coxsackie adenovirus receptor

dATP:

deoxyadenosine triphosphate

DbpA:

DNA binding protein A

ESAM:

endothelial cell-selective adhesion molecule

FRAP:

fluorescence recovery after photobleaching

FRET:

fluorescence resonance energy transfer

GAP:

GTPase activating protein

GEF:

guanine nucleotide exchange factor

GUK:

guanylate kinase (domain)

JAM:

junction associated molecule

MAGI:

membrane-associated guanylate kinase with Inverted orientation

MDCK:

Madin Darby Canine Kidney

MLCK:

myosin light chain kinase

PALS:

protein associated with Lin-7

PAR:

partition-defective (gene/protein)

PATJ:

Pals1-associated tight junction protein

PDZ:

PSD-95/disks large/zonula occludens-1 (domain)

PLEKHA7:

Pleckstrin Homology Domain Containing A7

ROCK:

Rho-associated protein Kinase

SH3:

Src homology-3

TAMPS:

TJ-associated MARVEL proteins

TEER:

trans-epithelial electrical resistance

TJ:

tight junction

TNF:

tumor necrosis factor

ZA:

zonula adhaerens

ZO:

zonula occludens

ZO-1:

zonula-occludens-1 (protein)

ZO-2:

zonula-occludens-2 (protein)

ZO-3:

zonula-occludens-3 (protein)

ZONAB:

ZO-1–associated nucleic acid binding protein

ZPSG:

ZO protein PDZ3-SH3-GUK (domains)

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Acknowledgments

I am grateful to Sophie Sluysmans, Ekaterina Vasileva, Florian Rouaud, and Jimit Shah for comments on the manuscript. The Citi laboratory is supported by the Swiss National Foundation, the State of Geneva, and the Novartis Foundation.

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  1. Department of Cell Biology, Faculty of Sciences, University of Geneva, 1211-4, Geneva, Switzerland

    Sandra Citi

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Citi, S. The mechanobiology of tight junctions. Biophys Rev 11, 783–793 (2019). https://doi.org/10.1007/s12551-019-00582-7

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