001     276854
005     20250225092624.0
024 7 _ |a 10.1073/pnas.1611684114
|2 doi
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|2 pmc
024 7 _ |a 0027-8424
|2 ISSN
024 7 _ |a 1091-6490
|2 ISSN
037 _ _ |a DZNE-2025-00367
041 _ _ |a English
082 _ _ |a 500
100 1 _ |a Milatz, Susanne
|0 0000-0001-9893-0473
|b 0
245 _ _ |a Mosaic expression of claudins in thick ascending limbs of Henle results in spatial separation of paracellular Na+ and Mg2+ transport.
260 _ _ |a Washington, DC
|c 2017
|b National Acad. of Sciences
336 7 _ |a article
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336 7 _ |a ARTICLE
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520 _ _ |a The thick ascending limb (TAL) of Henle's loop drives paracellular Na+, Ca2+, and Mg2+ reabsorption via the tight junction (TJ). The TJ is composed of claudins that consist of four transmembrane segments, two extracellular segments (ECS1 and -2), and one intracellular loop. Claudins interact within the same (cis) and opposing (trans) plasma membranes. The claudins Cldn10b, -16, and -19 facilitate cation reabsorption in the TAL, and their absence leads to a severe disturbance of renal ion homeostasis. We combined electrophysiological measurements on microperfused mouse TAL segments with subsequent analysis of claudin expression by immunostaining and confocal microscopy. Claudin interaction properties were examined using heterologous expression in the TJ-free cell line HEK 293, live-cell imaging, and Förster/FRET. To reveal determinants of interaction properties, a set of TAL claudin protein chimeras was created and analyzed. Our main findings are that (i) TAL TJs show a mosaic expression pattern of either cldn10b or cldn3/cldn16/cldn19 in a complex; (ii) TJs dominated by cldn10b prefer Na+ over Mg2+, whereas TJs dominated by cldn16 favor Mg2+ over Na+; (iii) cldn10b does not interact with other TAL claudins, whereas cldn3 and cldn16 can interact with cldn19 to form joint strands; and (iv) further claudin segments in addition to ECS2 are crucial for trans interaction. We suggest the existence of at least two spatially distinct types of paracellular channels in TAL: a cldn10b-based channel for monovalent cations such as Na+ and a spatially distinct site for reabsorption of divalent cations such as Ca2+ and Mg2.
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588 _ _ |a Dataset connected to CrossRef, PubMed, , Journals: pub.dzne.de
650 _ 7 |a FRET
|2 Other
650 _ 7 |a claudin interaction
|2 Other
650 _ 7 |a microperfusion
|2 Other
650 _ 7 |a paracellular ion transport
|2 Other
650 _ 7 |a tight junction
|2 Other
650 _ 7 |a Claudins
|2 NLM Chemicals
650 _ 7 |a Sodium
|0 9NEZ333N27
|2 NLM Chemicals
650 _ 7 |a Magnesium
|0 I38ZP9992A
|2 NLM Chemicals
650 _ 2 |a Animals
|2 MeSH
650 _ 2 |a Claudins: genetics
|2 MeSH
650 _ 2 |a Claudins: metabolism
|2 MeSH
650 _ 2 |a HEK293 Cells
|2 MeSH
650 _ 2 |a Humans
|2 MeSH
650 _ 2 |a Loop of Henle: metabolism
|2 MeSH
650 _ 2 |a Loop of Henle: physiology
|2 MeSH
650 _ 2 |a Magnesium: metabolism
|2 MeSH
650 _ 2 |a Mice, Inbred C57BL
|2 MeSH
650 _ 2 |a Mice, Knockout
|2 MeSH
650 _ 2 |a Rats, Sprague-Dawley
|2 MeSH
650 _ 2 |a Sodium: metabolism
|2 MeSH
650 _ 2 |a Tight Junctions: metabolism
|2 MeSH
700 1 _ |a Himmerkus, Nina
|0 0000-0002-2910-6728
|b 1
700 1 _ |a Wulfmeyer, Vera Christine
|b 2
700 1 _ |a Drewell, Hoora
|b 3
700 1 _ |a Mutig, Kerim
|b 4
700 1 _ |a Hou, Jianghui
|b 5
700 1 _ |a Breiderhoff, Tilman
|0 P:(DE-2719)9003035
|b 6
|u dzne
700 1 _ |a Müller, Dominik
|b 7
700 1 _ |a Fromm, Michael
|b 8
700 1 _ |a Bleich, Markus
|b 9
700 1 _ |a Günzel, Dorothee
|b 10
773 _ _ |a 10.1073/pnas.1611684114
|g Vol. 114, no. 2
|0 PERI:(DE-600)1461794-8
|n 2
|p E219 - E227
|t Proceedings of the National Academy of Sciences of the United States of America
|v 114
|y 2017
|x 0027-8424
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