Activation of a polyvalent cation-sensing receptor decreases magnesium transport via claudin-16.

Activation of a polyvalent cation-sensing receptor decreases magnesium transport via claudin-16. Research Abstract Details 

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Activation of a polyvalent cation-sensing receptor decreases magnesium transport via claudin-16. Abstract Text:

Akira Ikari,Chiaki Okude,Hayato Sawada,Yohei Sasaki,Yasuhiro Yamazaki,Junko Sugatani,Masakuni Degawa,Masao Miwa,

Renal magnesium is mainly reabsorbed by a paracellular pathway in the thick ascending limb of Henle. The expression of claudin-16 increased magnesium transport in Madin-Darby canine kidney (MDCK) cells. Little is known about the regulatory mechanism of magnesium transport via claudin-16. Here we examined the effect of a polyvalent cation-sensing receptor (CaSR) on the intracellular distribution of and transport of magnesium by claudin-16. FLAG-tagged claudin-16 was stably expressed in MDCK cells using a Tet-OFF system. The activation of CaSR by magnesium, calcium, neomycin, and gadolinium did not affect the expression of FLAG-tagged claudin-16, CaSR, or ZO-1, a tight junctional scaffolding protein. These activators decreased the phosphoserine level of FLAG-tagged claudin-16 and the association of FLAG-tagged claudin-16 with ZO-1. The activation of CaSR induced a decrease in PKA activity. Immunofluorescence microscopy revealed that FLAG-tagged claudin-16 is distributed at the cell-cell border under unstimulated conditions, whereas it translocates to the intracellular compartment, mainly lysosome, with the activation of CaSR. In contrast, the distribution of ZO-1 was unaffected by the activation. The expression of FLAG-tagged claudin-16 increased transepithelial electrical resistance (TER) and transepithelial magnesium transport without affecting FITC-dextran (MW 4000) flux. The activation of CaSR decreased TER and magnesium transport, which were recovered by co-treatment with dibutyryl cAMP, a membrane-permeable cAMP analogue. Taken together, CaSR activation may decrease PKA activity, resulting in a decrease in phosphorylated claudin-16, the translocation of claudin-16 to lysosome and a decrease in magnesium reabsorption.

Activation of a polyvalent cation-sensing receptor decreases magnesium transport via claudin-16. Publishing Authors By Initials

A Ikari,C Okude,H Sawada,Y Sasaki,Y Yamazaki,J Sugatani,M Degawa,M Miwa,

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Activation of a polyvalent cation-sensing receptor decreases magnesium transport via claudin-16. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: Biochimica et biophysica acta

VOLUME: 1778

Page Numbers: 283-90

Journal Abbreviation: Biochim. Biophys. Acta

ISSN: 0006-3002

DAY: 12

MONTH: 10

YEAR: 2007

Activation of a polyvalent cation-sensing receptor decreases magnesium transport via claudin-16. Information

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LANGUAGE: eng

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Grant and Affiliation Information for Activation of a polyvalent cation-sensing receptor decreases magnesium transport via claudin-16.

AFFILIATION: Department of Pharmaco-Biochemistry, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan.

Country: Netherlands

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MEDLINETA: Biochim Biophys Acta

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