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Acta Physiol (Oxf). 2019 Jun 12:e13334. doi: 10.1111/apha.13334. [Epub ahead of print]

Claudin-15 forms a water channel through the tight junction with distinct function compared to claudin-2.

Author information

1
Department of Gastroenterology, Rheumatology and Infectious Diseases, Institute of Clinical Physiology/Nutritional Medicine, Charité - Universitätsmedizin Berlin, Berlin, Germany.

Abstract

AIM:

Claudin-15 is mainly expressed in the small intestine and indirectly involved in glucose absorption. Similar to claudin-2 and -10b, claudin-15 is known to form a paracellular channel for small cations. Claudin-2, but not claudin-10b, also forms water channels. Here we experimentally tested whether claudin-15 also mediates water transport and if yes, whether water transport is Na+ -coupled, as seen for claudin-2.

METHODS:

MDCK C7 cells were stably transfected with claudin-15. Ion and water permeability were investigated in confluent monolayers of control and claudin-15-expressing cells. Water flux was induced by an osmotic or ionic gradient.

RESULTS:

Expression of claudin-15 in MDCK cells strongly increased cation permeability. The permeability ratios for monovalent cations indicated a passage of partially hydrated ions through the claudin-15 pore. Accordingly, its pore diameter was determined to be larger than that of claudin-2 and claudin-10b. Mannitol-induced water flux was elevated in claudin-15-expressing cells compared to control cells. In contrast to the Na+ -coupled water flux of claudin-2 channels, claudin-15-mediated water flux was inhibited by Na+ flux. Consequently, water flux was increased in Na+ -free solution. Likewise, Na+ flux was decreased after induction of water flux through claudin-15.

CONCLUSION:

Claudin-15, similar to claudin-2, forms a paracellular cation and water channel. In functional contrast to claudin-2, water and Na+ fluxes through claudin-15 inhibit each other. Claudin-15 allows Na+ to retain part of its hydration shell within the pore. This then reduces the simultaneous passage of additional water through the pore.

KEYWORDS:

claudin-15 pore diameter; paracellular ion permeability; paracellular water permeability

PMID:
31188544
DOI:
10.1111/apha.13334

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