Regulated transport of sulfate and oxalate by SLC26A2/DTDST
Regulated transport of sulfate and oxalate by SLC26A2/DTDST
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DOI：
10.1152/ajpcell.00004.2010
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发表时间：
2010-06-01
影响因子：
5.5
通讯作者：
Alper, Seth L.
中科院分区：
文献类型：
--
作者：
Heneghan, John F.;Akhavein, Arash;Alper, Seth L.
首页--期刊主要分类--期刊细介绍--期刊题录与文摘--期刊详细文摘内容SLC26A2/DTDST调控硫酸盐和草酸的运输。Am J Physiol Cell Physiol 298：C1363-C1375,2010。2010年3月10日首次发表；SLC26a6(-/-)小鼠的doi:10.1152/ajpcell.00004.2010.-Nephrolithiasis伴随着肠道草酸分泌减少50%-75%，而肠道草酸吸收没有变化。肠细胞草酸吸收途径和SLc26a6非依赖性草酸分泌途径的分子同一性仍不明确。已报道的SO42转运体SLC26A2在肠道中的表达促使我们研究了在非洲爪哇卵母细胞中表达的人SLC26A2和小鼠SLC26A2对草酸和其他阴离子的转运。我们发现hSLC26A2介导的[C-14]草酸摄取(K-1/2为0.65+/-0.08 mM)被外部SO42-(K-1/2为3.1 mM)顺式抑制。HSLC26A2介导的双向草酸/SO42-交换显示胞外SO42-K-1/2与胞内[C-14]草酸交换的SO42-K-1/2为1.58+/-0.44 mM，与胞内35SO(4)(2-)交换的胞外草酸K-1/2为0.14+/-0.11 mM。MSLc26a2的内流速率和K-1/2值相似。HSLC26A2介导的草酸/氯离子交换和双向SO42-/氯离子交换不能被检测到。两个SLC26A2同源基因对胞内[C-14]草酸、(SO42-)-S-35或氯-36(-)的外流都表现出非饱和的胞外氯离子依赖性。Cl-36(-)外流到胞外Cl-、SO42-和草酸的速率常数均比反向交换低10倍。酸性胞外pH(pH(O))抑制hSLC26A2介导的所有模式的阴离子交换。相反，酸性胞内pH(pH(I))选择性地激活胞外Cl-与胞内(SO42-)-S-35的交换，而不激活胞内Cl36(-)或[C-14]草酸的交换。蛋白激酶C通过降低hSLC26A2的表面丰度来抑制其活性。HSLC26A2的营养不良突变体R279W和A386V对35SO(4)(2-)和[C-14]草酸的摄取减少程度相似。A386V表面丰度降低，但R279W表面丰度处于野生型水平。
Heneghan JF, Akhavein A, Salas MJ, Shmukler BE, Karniski LP, Vandorpe DH, Alper SL. Regulated transport of sulfate and oxalate by SLC26A2/DTDST. Am J Physiol Cell Physiol 298: C1363-C1375, 2010. First Published March 10, 2010; doi:10.1152/ajpcell.00004.2010.-Nephrolithiasis in the Slc26a6(-/-) mouse is accompanied by 50-75% reduction in intestinal oxalate secretion with unchanged intestinal oxalate absorption. The molecular identities of enterocyte pathways for oxalate absorption and for Slc26a6-independent oxalate secretion remain undefined. The reported intestinal expression of SO42- transporter SLC26A2 prompted us to characterize transport of oxalate and other anions by human SLC26A2 and mouse Slc26a2 expressed in Xenopus oocytes. We found that hSLC26A2- mediated [C-14]oxalate uptake (K-1/2 of 0.65 +/- 0.08 mM) was cis-inhibited by external SO42- (K-1/2 of 3.1 mM). hSLC26A2-mediated bidirectional oxalate/SO42- exchange exhibited extracellular SO42- K-1/2 of 1.58 +/- 0.44 mM for exchange with intracellular [C-14]oxalate, and extracellular oxalate K-1/2 of 0.14 +/- 0.11 mM for exchange with intracellular 35SO(4)(2-). Influx rates and K-1/2 values for mSlc26a2 were similar. hSLC26A2- mediated oxalate/Cl- exchange and bidirectional SO42-/Cl- exchange were not detectably electrogenic. Both SLC26A2 orthologs exhibited nonsaturable extracellular Cl- dependence for efflux of intracellular [C-14]oxalate, (SO42-)-S-35, or Cl-36(-). Rate constants for Cl-36(-) efflux into extracellular Cl-, SO42-, and oxalate were uniformly 10-fold lower than for oppositely directed exchange. Acidic extracellular pH (pH(o)) inhibited all modes of hSLC26A2-mediated anion exchange. In contrast, acidic intracellular pH (pH(i)) selectively activated exchange of extracellular Cl- for intracellular (SO42-)-S-35 but not for intracellular Cl-36(-) or [C-14]oxalate. Protein kinase C inhibited hSLC26A2 by reducing its surface abundance. Diastrophic dysplasia mutants R279W and A386V of hSLC26A2 exhibited similar reductions in uptake of both 35SO(4)(2-) and [C-14]oxalate. A386V surface abundance was reduced, but R279W surface abundance was at wild-type levels.