Myosin light chain phosphorylation regulates barrier function by remodeling tight junction structure
Abstract
Epithelial tight junctions form a barrier against passive paracellular flux. This barrier is regulated by complex physiologic and pathophysiologic signals that acutely fine-tune tight junction permeability. Although actomyosin contraction and myosin light chain phosphorylation are clearly involved in some forms of tight junction regulation, the contributions of other signaling events and the role of myosin light chain phosphorylation in this response are poorly understood. Here we ask if activation of myosin light chain kinase alone is sufficient to induce downstream tight junction regulation. We use a confluent polarized intestinal epithelial cell model system in which constitutively active myosin light chain kinase, tMLCK, is expressed using an inducible promoter. tMLCK expression increases myosin light chain phosphorylation, reorganizes perijunctional F-actin, and increases tight junction permeability. TJ proteins ZO-1 and occludin are markedly redistributed, morphologically and biochemically, but effects on claudin-1 and claudin-2 are limited. tMLCK inhibition prevents changes in barrier function and tight junction organization induced by tMLCK expression, suggesting that these events both require myosin light chain phosphorylation. We conclude that myosin light chain phosphorylation alone is sufficient to induce tight junction regulation and provide new insights into the molecular mechanisms that mediate this regulation.
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The leak pathway is believed to be regulated by myosin light-chain kinase, where constitutively active MLCK is sufficient to increase the leak pathway-dependent permeability both in vitro and in vivo.
“The leak pathway is believed to be regulated by myosin light-chain kinase (MLCK), where constitutively active MLCK is sufficient to increase the leak pathway–dependent permeability both in vitro and in vivo.52,53”
From Regulation of Intestinal Barrier Function by Microbial Metabolites (2021) · cites this paper as [52]
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- Authors
- Shen, L., Black, E. D., Witkowski, E. D., Lencer, W. I., Guerriero, V., Schneeberger, E. E., & Turner, J. R.
- Affiliations
- University of Chicago (US)
- Harvard University (US)
- University of Arizona (US)
- Venue
- Journal of Cell Science
- Publisher
- The Company of Biologists
- Published
- 2006-05-15
- Volume
- 119
- Issue
- 10
- Pages
- 2095-2106
- ISSN
- 0021-9533 (ISSN-L)
- 1477-9137
- OpenAlex
- W2052532027
- Cited by
- 467
- References
- 75
- Citations by year
- 2026: 13 · 2025: 18 · 2024: 22 · 2023: 24 · 2022: 26 · 2021: 34 · 2020: 24 · 2019: 30 · 2018: 19 · 2017: 26 · 2016: 25 · 2015: 33 · 2014: 11 · 2013: 24 · 2012: 35
- FWCI
- 11.61
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Cell Science (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Heart, Lung, and Blood Institute (HL 36781, R01HL036781, HL-25822, R01HL025822)
- National Cancer Institute (CA 14599, P30CA014599)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK57827, DK-68271, DK53056, DK 48106, DK61931, R01DK057827, DK42086, P30DK042086, R01DK068271, R01DK061931)
- Topics
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion Transport and Channel Regulation
- Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
- Keywords
- myosin light chain phosphorylation, myosin light chain kinase, tight junctions, epithelial barrier function, tight junction permeability, intestinal epithelial cells, F-actin reorganization, ZO-1, occludin, claudin-1, claudin-2, actomyosin contraction
- MeSH terms
- Actins, Cell Membrane Permeability, Enzyme Induction, Epithelium, Humans, Membrane Proteins, Microscopy, Fluorescence, Myosin-Light-Chain Kinase, Phosphoproteins, Phosphorylation, Caco-2 Cells, Myosin Light Chains, Tight Junctions, Claudins, Claudin-1, Occludin, Zonula Occludens-1 Protein
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
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