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@ARTICLE{Milatz:276854,
      author       = {Milatz, Susanne and Himmerkus, Nina and Wulfmeyer, Vera
                      Christine and Drewell, Hoora and Mutig, Kerim and Hou,
                      Jianghui and Breiderhoff, Tilman and Müller, Dominik and
                      Fromm, Michael and Bleich, Markus and Günzel, Dorothee},
      title        = {{M}osaic expression of claudins in thick ascending limbs of
                      {H}enle results in spatial separation of paracellular {N}a+
                      and {M}g2+ transport.},
      journal      = {Proceedings of the National Academy of Sciences of the
                      United States of America},
      volume       = {114},
      number       = {2},
      issn         = {0027-8424},
      address      = {Washington, DC},
      publisher    = {National Acad. of Sciences},
      reportid     = {DZNE-2025-00367},
      pages        = {E219 - E227},
      year         = {2017},
      abstract     = {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.},
      keywords     = {Animals / Claudins: genetics / Claudins: metabolism /
                      HEK293 Cells / Humans / Loop of Henle: metabolism / Loop of
                      Henle: physiology / Magnesium: metabolism / Mice, Inbred
                      C57BL / Mice, Knockout / Rats, Sprague-Dawley / Sodium:
                      metabolism / Tight Junctions: metabolism / FRET (Other) /
                      claudin interaction (Other) / microperfusion (Other) /
                      paracellular ion transport (Other) / tight junction (Other)
                      / Claudins (NLM Chemicals) / Sodium (NLM Chemicals) /
                      Magnesium (NLM Chemicals)},
      ddc          = {500},
      pnm          = {899 - ohne Topic (POF4-899)},
      pid          = {G:(DE-HGF)POF4-899},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:28028216},
      pmc          = {pmc:PMC5240732},
      doi          = {10.1073/pnas.1611684114},
      url          = {https://pub.dzne.de/record/276854},
}