Ruknudin Abdul M, Wei Shao-Kui, Haigney Mark C, Lederer W J, Schulze Dan H
Department of Microbiology and Immunology, 660 W. Redwood Street, Baltimore, MD 21201, USA.
Ann N Y Acad Sci. 2007 Mar;1099:103-18. doi: 10.1196/annals.1387.036.
The Na+/Ca2+ exchanger (NCX) is an important Ca2+ transport mechanism in virtually all cells in the body. There are three genes that control the expression of NCX in mammals. There are at least 16 alternatively spliced isoforms of NCX1 that target muscle and nerve and other tissues. Here we briefly discuss three remarkable regulatory issues or "conundrums" that involve the most prevalently expressed gene, NCX1. (1) How is NCX1 regulated by phosphorylation? We suggest that the macromolecular complex of NCX1 plays a critical role in the regulation of NCX. The role of the macromolecular complex and evidence supporting its existence and functional importance is presented. (2) Can there be transport block of a single "mode" of NCX1 transport by drugs or therapeutic agents? The simple answer is "no." A brief explanation is provided. (3) How can NCX1 knockout mice live? The answer is "by other compensatory regulatory mechanisms." These conundrums highlight important features in NCX1 and lay the foundation for new experiments to elucidate function and regulation of NCX1 and provide a context for investigations that seek to understand novel therapeutic agents.
钠钙交换体（NCX）是机体几乎所有细胞中一种重要的钙转运机制。在哺乳动物中，有三个基因控制NCX的表达。NCX1至少有16种可变剪接异构体，其作用于肌肉、神经和其他组织。在此，我们简要讨论三个显著的调控问题或“谜题”，这些问题涉及表达最普遍的基因NCX1。（1）NCX1如何通过磷酸化进行调控？我们认为，NCX1的大分子复合物在NCX的调控中起关键作用。本文介绍了大分子复合物的作用以及支持其存在和功能重要性的证据。（2）药物或治疗剂能否阻断NCX1单一“模式”的转运？简单的答案是“不能”。本文提供了简要解释。（3）NCX1基因敲除小鼠如何存活？答案是“通过其他代偿性调控机制”。这些谜题突出了NCX1的重要特征，为阐明NCX1功能和调控的新实验奠定了基础，并为旨在了解新型治疗剂的研究提供了背景。
