Polarization of Na(+)/H(+) and Cl(-)/HCO (3)(-) exchangers in migrating renal epithelial cells.

Polarization of Na(+)/H(+) and Cl(-)/HCO (3)(-) exchangers in migrating renal epithelial cells.
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Na(+)/H(+)和Cl( - )/HCO(3)( - )交换器的极化。

DOI:
10.1085/jgp.115.5.599
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发表时间:
2000-05
影响因子:
3.8
通讯作者:
Schwab, A
Schwab, A
中科院分区:
医学2区
文献类型:
--
作者:
Klein, M;Seeger, P;Schuricht, B;Alper, SL;Schwab, A

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细胞迁移对于免疫防御、伤口愈合或肿瘤转移形成等过程至关重要。通常,迁移细胞在运动平面内极化,片状伪足和细胞体分别代表细胞的前部和后部。在这里,我们解决了这种极化是否也延伸到迁移细胞质膜中离子转运蛋白(例如 Na+/H+ 交换器(NHE)和阴离子交换器)的分布的问题。肾上皮细胞(Madin-Darby 犬肾,MDCK-F)和人黑色素瘤细胞的运动需要两种转运蛋白,因为它们的阻断会以剂量依赖性方式降低迁移率。 NHE 阻滞剂对 MDCK-F 细胞迁移的抑制伴随着 pHi 的降低。然而,当细胞用弱有机酸酸化时,MDCK-F 细胞的迁移是正常的,尽管 pHi 下降更为明显。在这些条件下,NHE 活性增加,细胞因有机阴离子和 Na+ 的积累而肿胀。当专门应用于片状伪足时,NHE 或阴离子交换阻滞剂抑制 MDCK-F 细胞的迁移与应用于整个细胞表面时一样有效。当它们被引导至细胞体时,迁移不受影响。这些数据通过免疫细胞化学得到证实,因为阴离子交换剂AE2集中在MDCK-F细胞的前端。我们的研究结果表明,NHE 和阴离子交换剂在迁移细胞中以极化方式分布。它们与两种转运蛋白通过溶质摄取和随后迁移细胞前端的体积增加对片状足突出的重要贡献一致。
Cell migration is crucial for processes such as immune defense, wound healing, or the formation of tumor metastases. Typically, migrating cells are polarized within the plane of movement with lamellipodium and cell body representing the front and rear of the cell, respectively. Here, we address the question of whether this polarization also extends to the distribution of ion transporters such as Na+/H+ exchanger (NHE) and anion exchanger in the plasma membrane of migrating cells. Both transporters are required for locomotion of renal epithelial (Madin-Darby canine kidney, MDCK-F) cells and human melanoma cells since their blockade reduces the rate of migration in a dose-dependent manner. Inhibition of migration of MDCK-F cells by NHE blockers is accompanied by a decrease of pHi. However, when cells are acidified with weak organic acids, migration of MDCK-F cells is normal despite an even more pronounced decrease of pHi. Under these conditions, NHE activity is increased so that cells are swelling due to the accumulation of organic anions and Na+. When exclusively applied to the lamellipodium, blockers of NHE or anion exchange inhibit migration of MDCK-F cells as effectively as when applied to the entire cell surface. When they are directed to the cell body, migration is not affected. These data are confirmed immunocytochemically in that the anion exchanger AE2 is concentrated at the front of MDCK-F cells. Our findings show that NHE and anion exchanger are distributed in a polarized way in migrating cells. They are consistent with important contributions of both transporters to protrusion of the lamellipodium via solute uptake and consequent volume increase at the front of migrating cells.
DOI: 10.1002/cm.970100409
发表时间: 1988-01-01
影响因子: --
作者:
BEREITERHAHN, J;VOTH, M
通讯作者: VOTH, M
DOI: 10.1074/jbc.270.25.15222
发表时间: 1995-06-23
影响因子: 4.8
作者:
EDMONDS, BT;MURRAY, J;CONDEELIS, J
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DOI: 10.1016/s0006-3495(92)81938-0
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影响因子: 3.4
作者:
ITO, T;SUZUKI, A;STOSSEL, TP
通讯作者: STOSSEL, TP
DOI: 10.1007/s004240050943
发表时间: 2000-01-01
影响因子: 4.5
作者:
Schneider, SW;Pagel, P;Schwab, A
通讯作者: Schwab, A
DOI: 10.1083/jcb.138.4.927
发表时间: 1997-08-25
期刊: The Journal of cell biology
影响因子: --
作者:
Mackay DJ;Esch F;Furthmayr H;Hall A
通讯作者: Hall A