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溶质载体家族 10(SLC10):超越胆汁酸转运。

The solute carrier family 10 (SLC10): beyond bile acid transport.

机构信息

Department of Pharmaceutical Sciences, University of Maryland, Baltimore, MD 21201, USA.

出版信息

Mol Aspects Med. 2013 Apr-Jun;34(2-3):252-69. doi: 10.1016/j.mam.2012.07.004.

Abstract

The solute carrier (SLC) family 10 (SLC10) comprises influx transporters of bile acids, steroidal hormones, various drugs, and several other substrates. Because the seminal transporters of this family, namely, sodium/taurocholate cotransporting polypeptide (NTCP; SLC10A1) and the apical sodium-dependent bile acid transporter (ASBT; SLC10A2), were primarily bile acid transporters, the term "sodium bile salt cotransporting family" was used for the SLC10 family. However, this notion became obsolete with the finding of other SLC10 members that do not transport bile acids. For example, the sodium-dependent organic anion transporter (SOAT; SLC10A6) transports primarily sulfated steroids. Moreover, NTCP was shown to also transport steroids and xenobiotics, including HMG-CoA inhibitors (statins). The SLC10 family contains four additional members, namely, P3 (SLC10A3; SLC10A3), P4 (SLC10A4; SLC10A4), P5 (SLC10A5; SLC10A5) and SLC10A7 (SLC10A7), several of which were unknown or considered hypothetical until approximately a decade ago. While their substrate specificity remains undetermined, great progress has been made towards their characterization in recent years. Explicitly, SLC10A4 may participate in vesicular storage or exocytosis of neurotransmitters or mastocyte mediators, whereas SLC10A5 and SLC10A7 may be involved in solute transport and SLC10A3 may have a role as a housekeeping protein. Finally, the newly found role of bile acids in glucose and energy homeostasis, via the TGR5 receptor, sheds new light on the clinical relevance of ASBT and NTCP. The present mini-review provides a brief summary of recent progress on members of the SLC10 family.

摘要

溶质载体 (SLC) 家族 10 (SLC10) 包括胆汁酸、甾体激素、各种药物和其他几种底物的内流转运体。由于该家族的主要转运体,即牛磺胆酸钠共转运蛋白 (NTCP;SLC10A1) 和顶端钠依赖性胆汁酸转运体 (ASBT;SLC10A2),主要是胆汁酸转运体,因此该 SLC10 家族被称为“钠胆汁盐共转运家族”。然而,随着发现其他不转运胆汁酸的 SLC10 成员,这一概念已经过时。例如,钠依赖性有机阴离子转运体 (SOAT;SLC10A6) 主要转运硫酸化甾体。此外,NTCP 还被证明可以转运甾体和外源性物质,包括 HMG-CoA 抑制剂(他汀类药物)。SLC10 家族还包含四个额外的成员,即 P3(SLC10A3;SLC10A3)、P4(SLC10A4;SLC10A4)、P5(SLC10A5;SLC10A5)和 SLC10A7(SLC10A7),其中一些成员在大约十年前还不为人知或被认为是假设的。虽然它们的底物特异性尚未确定,但近年来在它们的特征描述方面取得了很大进展。具体而言,SLC10A4 可能参与神经递质或肥大细胞介质的囊泡储存或胞吐作用,而 SLC10A5 和 SLC10A7 可能参与溶质转运,SLC10A3 可能作为管家蛋白发挥作用。最后,通过 TGR5 受体发现胆汁酸在葡萄糖和能量稳态中的新作用,为 ASBT 和 NTCP 的临床相关性提供了新的启示。本综述简要总结了 SLC10 家族成员的最新进展。

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