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Claudin-15 forms a water channel through the tight junction with distinct function compared to claudin-2.
Acta Physiologica ( IF 6.3 ) Pub Date : 2019-07-08 , DOI: 10.1111/apha.13334
Rita Rosenthal 1 , Dorothee Günzel 1 , Jörg Piontek 1 , Susanne M Krug 1 , Carlos Ayala-Torres 1 , Caroline Hempel 1 , Dian Theune 1 , Michael Fromm 1
Affiliation  

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.

中文翻译:

与claudin-2相比,Claudin-15通过紧密连接形成一条水通道,具有独特的功能。

AIM Claudin-15主要在小肠中表达,间接参与葡萄糖吸收。与claudin-2和-10b相似,claudin-15已知会形成小阳离子的旁细胞通道。克劳丁2而不是克劳丁10b也形成水通道。在这里,我们通过实验测试了claudin-15是否也介导了水的运输,如果是,水的运输是否是Na +偶联的(如claudin-2所示)。方法用claudin-15稳定转染MDCK C7细胞。在对照和表达claudin-15的融合细胞单层中研究了离子和水的渗透性。通过渗透或离子梯度诱导水通量。结果claudin-15在MDCK细胞中的表达大大增加了阳离子的通透性。单价阳离子的渗透率表明部分水合离子通过claudin-15孔。因此,确定其孔径大于claudin-2和claudin-10b的孔径。与对照细胞相比,在表达claudin-15的细胞中甘露醇诱导的水通量升高。与claudin-2通道的Na +耦合水通量相比,claudin-15介导的水通量受Na +通量抑制。因此,在无Na +的溶液中水通量增加了。同样,通过claudin-15诱导水通量后,Na +通量降低。结论Claudin-15与claudin-2类似,可形成细胞旁阳离子和水通道。与claudin-2的功能相反,通过claudin-15的水和Na +通量相互抑制。Claudin-15允许Na +将其水合壳的一部分保留在孔中。
更新日期:2019-11-18
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