Regulation of the intestinal anion exchanger DRA (downregulated in adenoma).
Regulation of the intestinal anion exchanger DRA (downregulated in adenoma).
复制标题
肠道阴离子交换剂 DRA 的调节（在腺瘤中下调）。
DOI：
10.1111/j.1749-6632.2009.04044.x
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发表时间：
2009
影响因子：
5.2
通讯作者：
Gregor,Michael
中科院分区：
文献类型：
--
作者：
Lamprecht,Georg;Gaco,Vera;Turner,JerroldR;Natour,Dorgam;Gregor,Michael
屏障功能和跨上皮转运密切相关，有时平行干扰。NHE 3（在腺瘤中下调）是一种肠氯/碳酸氢盐交换器，在上胃肠道中与CFTR（囊性纤维化跨膜调节因子）功能性偶联以介导氯和碳酸氢盐分泌，在下胃肠道中与NHE 3（Na/H交换器亚型3）功能性偶联以介导电中性NaCl吸收。所有三种转运蛋白均具有PDZ结构域结合基序，其促进与衔接蛋白的NHERF（Na/H交换调节因子）家族成员[NHERF、E3 KARP（NHE 3激酶A调节蛋白）、PDZK 1（PDZ蛋白肾1）和IKEPP（肠和肾富集的PDZ蛋白）]的结合。调节的转运蛋白依赖于伴侣转运蛋白的存在，这可能涉及组装不同的复合物的转运蛋白，衔接蛋白，和信号分子。我们已经在HEK细胞中建立了稳定的表达。在这些不表达大量CFTR或NHE 3的细胞中，CFTR被细胞内钙抑制，但不被蛋白激酶C或蛋白激酶A抑制。在由4 Br-A23187诱导的高钙浓度下，这种抑制作用不依赖于PDZ的相互作用。这些数据表明，ESTs可以被单独调节，并且可以在更生理相关的表达系统（即，Caco-2/BBE细胞）中使用细胞内钙信号的天然激动剂。
Barrier function and transepithelial transport are intimately linked and are sometimes disturbed in parallel. DRA (downregulated in adenoma) is an intestinal chloride/bicarbonate exchanger that is functionally coupled to CFTR (cystic fibrosis transmembrane regulator) in the upper gastrointestinal tract to mediate chloride and bicarbonate secretion and to NHE3 (Na/H exchanger‐ isoform 3) in the lower gastrointestinal tract to mediate electroneutral NaCl absorption. All three transport proteins possess PDZ domain binding motifs that facilitate binding to members of the NHERF (Na/H exchanger regulatory factor) family of adapter proteins [NHERF, E3KARP (NHE3 kinase A regulatory protein), PDZK1 (PDZ protein kidney 1) and IKEPP (intestinal and kidney enriched PDZ protein)]. Regulation of DRA appears to depend on the presence of a partner transport protein, and this may involve the assembly of different complexes of transporters, adapter proteins, and signaling molecules. We have established stable expression of DRA in HEK cells. In these cells, that do not express significant amounts of CFTR or NHE3, DRA is inhibited by intracellular calcium but not by protein kinase C or protein kinase A. At high calcium concentrations induced by 4Br‐A23187 this inhibition is independent of the PDZ interaction of DRA. These data show that DRA can be individually regulated and may be confirmed in a more physiologically relevant expression system (i.e., Caco‐2/BBE cells) using natural agonists of the intracellular calcium signal.