Governing effect of regulatory proteins for Cl−/HCO3− exchanger 2 activity

IF 3.3 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Channels Pub Date : 2016-02-08 DOI:10.1080/19336950.2015.1134068

Y. Jeong, J. Hong

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引用次数: 12

Abstract

ABSTRACT Anion exchanger 2 (AE2) has a critical role in epithelial cells and is involved in the ionic homeostasis such as Cl− uptake and HCO3− secretion. However, little is known about the regulatory mechanism of AE2. The main goal of the present study was to investigate potential regulators, such as spinophilin (SPL), inositol-1,4,5-trisphosphate [IP3] receptors binding protein released with IP3 (IRBIT), STE20/SPS1-related proline/alanine-rich kinase (SPAK) kinase, and carbonic anhydrase XII (CA XII). We found that SPL binds to AE2 and markedly increased the Cl−/HCO3− exchange activity of AE2. Especially SPL 1–480 domain is required for enhancing AE2 activity. For other regulatory components that affect the fidelity of fluid and HCO3− secretion, IRBIT and SPAK had no effect on the activity of AE2 and no protein-protein interaction with AE2. It has been proposed that CA activity is closely associated with AE activity. In this study, we provide evidence that the basolateral membrane-associated CA isoform CA XII significantly increased the activity of AE2 and co-localized with AE2 to the plasma membrane. Collectively, SPL and CA XII enhanced the Cl−/HCO3− exchange activity of AE2. The modulating action of these regulatory proteins could serve as potential therapeutic targets for secretory diseases mediated by AE2.

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调节蛋白对Cl−/HCO3−交换器2活性的调控作用

阴离子交换剂2 (AE2)在上皮细胞中起关键作用，参与离子稳态，如Cl -摄取和HCO3 -分泌。然而，对AE2的调控机制知之甚少。本研究的主要目的是研究潜在的调节因子，如spinophilin (SPL)，肌醇-1,4,5-三磷酸[IP3]受体结合蛋白与IP3释放(IRBIT)， STE20/ sps1相关的脯氨酸/丙氨酸激酶(SPAK)激酶和碳酸酐酶XII (CA XII)。我们发现SPL与AE2结合并显著提高AE2的Cl - /HCO3 -交换活性。特别是SPL 1-480结构域是增强AE2活性所必需的。对于其他影响液体和HCO3−分泌保真度的调节成分，IRBIT和SPAK对AE2的活性没有影响，也没有与AE2的蛋白-蛋白相互作用。有人提出CA活性与AE活性密切相关。在这项研究中，我们提供的证据表明，基底外侧膜相关的CA异构体CA XII显著增加了AE2的活性，并与AE2共定位到质膜上。SPL和caxii共同增强了AE2的Cl−/HCO3−交换活性。这些调节蛋白的调节作用可作为AE2介导的分泌性疾病的潜在治疗靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Channels 生物-生化与分子生物学

CiteScore

5.90

自引率

0.00%

发文量

审稿时长

6-12 weeks

期刊介绍： Channels is an open access journal for all aspects of ion channel research. The journal publishes high quality papers that shed new light on ion channel and ion transporter/exchanger function, structure, biophysics, pharmacology, and regulation in health and disease. Channels welcomes interdisciplinary approaches that address ion channel physiology in areas such as neuroscience, cardiovascular sciences, cancer research, endocrinology, and gastroenterology. Our aim is to foster communication among the ion channel and transporter communities and facilitate the advancement of the field.