Nanoscale segregation of channel and barrier claudins enables paracellular ion flux.


Journal

Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555

Informations de publication

Date de publication:
25 08 2022
Historique:
received: 06 08 2021
accepted: 04 08 2022
entrez: 25 8 2022
pubmed: 26 8 2022
medline: 30 8 2022
Statut: epublish

Résumé

The paracellular passage of ions and small molecules across epithelia is controlled by tight junctions, complex meshworks of claudin polymers that form tight seals between neighboring cells. How the nanoscale architecture of tight junction meshworks enables paracellular passage of specific ions or small molecules without compromising barrier function is unknown. Here we combine super-resolution stimulated emission depletion microscopy in live and fixed cells and tissues, multivariate classification of super-resolution images and fluorescence resonance energy transfer to reveal the nanoscale organization of tight junctions formed by mammalian claudins. We show that only a subset of claudins can assemble into characteristic homotypic meshworks, whereas tight junctions formed by multiple claudins display nanoscale organization principles of intermixing, integration, induction, segregation, and exclusion of strand assemblies. Interestingly, channel-forming claudins are spatially segregated from barrier-forming claudins via determinants mainly encoded in their extracellular domains also known to harbor mutations leading to human diseases. Electrophysiological analysis of claudins in epithelial cells suggests that nanoscale segregation of distinct channel-forming claudins enables barrier function combined with specific paracellular ion flux across tight junctions.

Identifiants

pubmed: 36008380
doi: 10.1038/s41467-022-32533-4
pii: 10.1038/s41467-022-32533-4
pmc: PMC9411157
doi:

Substances chimiques

Claudins 0
Ions 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

4985

Informations de copyright

© 2022. The Author(s).

Références

J Cell Biol. 1973 Aug;58(2):390-400
pubmed: 4199658
Biochem J. 2005 Apr 15;387(Pt 2):553-60
pubmed: 15500448
BMC Genomics. 2015 Nov 16;16:944
pubmed: 26572553
Elife. 2015 Nov 14;4:e09906
pubmed: 26568313
Eur J Cell Biol. 1999 Dec;78(12):849-55
pubmed: 10669103
Proc Natl Acad Sci U S A. 2021 Nov 30;118(48):
pubmed: 34810264
Ann N Y Acad Sci. 2012 Jun;1257:77-84
pubmed: 22671592
Nat Commun. 2016 Jul 25;7:12276
pubmed: 27452368
J Cell Biol. 2001 Apr 16;153(2):263-72
pubmed: 11309408
Biochim Biophys Acta. 2008 Mar;1778(3):631-45
pubmed: 18036336
Eur J Cell Biol. 2010 Jul;89(7):547-56
pubmed: 20188437
Mol Biol Cell. 2008 May;19(5):1912-21
pubmed: 18287530
J Cell Biol. 2018 Jul 2;217(7):2373-2381
pubmed: 29720382
J Cell Sci. 2010 Jun 1;123(Pt 11):1913-21
pubmed: 20460438
Proc Natl Acad Sci U S A. 2017 Jan 10;114(2):E219-E227
pubmed: 28028216
Protoplasma. 1969;67(2):165-84
pubmed: 5346995
J Cell Biol. 2019 Oct 7;218(10):3372-3396
pubmed: 31467165
Biol Direct. 2006 Dec 08;1:37
pubmed: 17156438
J Cell Biol. 1998 Oct 19;143(2):391-401
pubmed: 9786950
Gastroenterology. 2011 Mar;140(3):913-23
pubmed: 20727355
J Gen Physiol. 2018 Jul 2;150(7):949-968
pubmed: 29915162
Nat Commun. 2019 Feb 18;10(1):816
pubmed: 30778075
J Cell Biol. 1999 Nov 15;147(4):891-903
pubmed: 10562289
J Mol Biol. 2020 Mar 27;432(7):2405-2427
pubmed: 32142789
Cell Mol Life Sci. 2011 Dec;68(23):3903-18
pubmed: 21533891
Proc Natl Acad Sci U S A. 2010 Apr 27;107(17):8011-6
pubmed: 20385797
Cold Spring Harb Perspect Biol. 2010 Jan;2(1):a002907
pubmed: 20182608
Microsc Res Tech. 2010 Oct;73(11):1019-29
pubmed: 20232465
J Cell Sci. 2009 May 15;122(Pt 10):1507-17
pubmed: 19383724
Science. 2014 Apr 18;344(6181):304-7
pubmed: 24744376
Proc Natl Acad Sci U S A. 2003 Apr 1;100(7):3971-6
pubmed: 12651952
Cell Mol Life Sci. 2012 Aug;69(16):2765-78
pubmed: 22402829
Proc Natl Acad Sci U S A. 1999 Jan 19;96(2):511-6
pubmed: 9892664
Am J Physiol Renal Physiol. 2006 Dec;291(6):F1288-99
pubmed: 16804102
J Am Soc Nephrol. 2022 Apr;33(4):699-717
pubmed: 35031570
Nat Methods. 2012 Jun 28;9(7):676-82
pubmed: 22743772
Proc Natl Acad Sci U S A. 2010 Oct 19;107(42):18010-5
pubmed: 20921420
Commun Biol. 2018 May 17;1:50
pubmed: 30271933
J Cell Biol. 1997 Jul 14;138(1):181-92
pubmed: 9214391
J Cell Biol. 2002 Mar 18;156(6):1099-111
pubmed: 11889141
Bioinformatics. 2013 Sep 15;29(18):2343-9
pubmed: 23836142
Am J Physiol Renal Physiol. 2020 May 1;318(5):F1138-F1146
pubmed: 32174144
J Clin Invest. 2008 Feb;118(2):619-28
pubmed: 18188451
Genet Med. 2018 Feb;20(2):190-201
pubmed: 28771254
Gastroenterology. 2013 Feb;144(2):369-380
pubmed: 23089202
J Cell Biol. 1986 Sep;103(3):755-66
pubmed: 3528172
J Cell Biol. 1998 Jun 29;141(7):1539-50
pubmed: 9647647
PLoS Genet. 2017 Jul 7;13(7):e1006897
pubmed: 28686597
Bioinformatics. 2016 Nov 15;32(22):3532-3534
pubmed: 27412086
Nucleic Acids Res. 2015 Jul 1;43(W1):W566-70
pubmed: 25969447
Biochim Biophys Acta Biomembr. 2020 Jul 1;1862(7):183279
pubmed: 32224152
Biochim Biophys Acta. 2010 Nov;1798(11):2048-57
pubmed: 20655293
Nat Rev Mol Cell Biol. 2016 Sep;17(9):564-80
pubmed: 27353478
Biochem J. 2015 Jun 15;468(3):449-58
pubmed: 25849148
J Biol Chem. 2014 Mar 14;289(11):7641-53
pubmed: 24478310
Nat Commun. 2016 Mar 04;7:10778
pubmed: 26940217
Int J Mol Sci. 2020 Jan 23;21(3):
pubmed: 31979366
J Biol Chem. 2014 Mar 7;289(10):6475-6484
pubmed: 24436330
Bioinformatics. 2011 Sep 1;27(17):2453-4
pubmed: 21727141
J Membr Biol. 1978 Mar 10;39(2-3):219-32
pubmed: 641977
Cell. 2019 Oct 31;179(4):923-936.e11
pubmed: 31675499
Physiol Rev. 2013 Apr;93(2):525-69
pubmed: 23589827
Mol Biol Cell. 2017 Feb 15;28(4):524-534
pubmed: 27974639
PLoS One. 2012;7(2):e31128
pubmed: 22319608
PLoS One. 2015 Mar 17;10(3):e0119869
pubmed: 25781928
J Cell Biol. 1963 May;17:375-412
pubmed: 13944428
J Cell Biol. 1999 Dec 13;147(6):1351-63
pubmed: 10601346
J Mol Biol. 2015 Jan 30;427(2):291-7
pubmed: 25451028
J Cell Sci. 2002 Dec 15;115(Pt 24):4969-76
pubmed: 12432083
Am J Physiol Cell Physiol. 2002 Jul;283(1):C142-7
pubmed: 12055082
J Cell Sci. 1995 Jan;108 ( Pt 1):127-42
pubmed: 7738090
Science. 1999 Jul 2;285(5424):103-6
pubmed: 10390358

Auteurs

Hannes Gonschior (H)

Leibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP), 13125, Berlin, Germany.

Christopher Schmied (C)

Leibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP), 13125, Berlin, Germany.

Rozemarijn Eva Van der Veen (RE)

Leibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP), 13125, Berlin, Germany.

Jenny Eichhorst (J)

Leibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP), 13125, Berlin, Germany.

Nina Himmerkus (N)

Institute of Physiology, Christian-Albrechts-Universität zu Kiel, 24118, Kiel, Germany.

Jörg Piontek (J)

Clinical Physiology/Nutritional Medicine, Medical Department, Division of Gastroenterology, Infectiology, Rheumatology, Charité - Universitätsmedizin Berlin, 12203, Berlin, Germany.

Dorothee Günzel (D)

Clinical Physiology/Nutritional Medicine, Medical Department, Division of Gastroenterology, Infectiology, Rheumatology, Charité - Universitätsmedizin Berlin, 12203, Berlin, Germany.

Markus Bleich (M)

Institute of Physiology, Christian-Albrechts-Universität zu Kiel, 24118, Kiel, Germany.

Mikio Furuse (M)

Division of Cell Structure, National Institute for Physiological Sciences, Okazaki, Aichi, 444-8787, Japan.
Department of Physiological Sciences, School of Life Science, SOKENDAI (Graduate University for Advanced Studies), Okazaki, Aichi, 444-8585, Japan.

Volker Haucke (V)

Leibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP), 13125, Berlin, Germany.
Faculty of Biology, Chemistry and Pharmacy, Freie Universität Berlin, 14195, Berlin, Germany.

Martin Lehmann (M)

Leibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP), 13125, Berlin, Germany. mlehmann@fmp-berlin.de.

Articles similaires

[Redispensing of expensive oral anticancer medicines: a practical application].

Lisanne N van Merendonk, Kübra Akgöl, Bastiaan Nuijen
1.00
Humans Antineoplastic Agents Administration, Oral Drug Costs Counterfeit Drugs

Smoking Cessation and Incident Cardiovascular Disease.

Jun Hwan Cho, Seung Yong Shin, Hoseob Kim et al.
1.00
Humans Male Smoking Cessation Cardiovascular Diseases Female
Humans United States Aged Cross-Sectional Studies Medicare Part C
1.00
Humans Yoga Low Back Pain Female Male

Classifications MeSH