Emanuel Strehler's work on calcium pumps and calcium signaling.
Emanuel Strehler's work on calcium pumps and calcium signaling.
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DOI：
10.4331/wjbc.v2.i4.67
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发表时间：
2011-04
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影响因子：
--
通讯作者：
E. Strehler
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作者：
E. Strehler
细胞具有严格控制游离钙（Ca（2+））的流入、流出和静息水平的机制。不适当的Ca（2+）信号传导和异常的Ca（2+）水平涉及许多临床疾病，包括心脏病、阿尔茨海默病和中风。Ca（2+）在细胞生长、分化和运动中也起着重要作用;这些过程中的干扰是细胞转化和癌症进展的基础。因此，Strehler实验室的研究重点是更好地理解确保细胞中适当Ca（2+）稳态所需的分子“工具包”，以及局部Ca（2+）信号传导的机制。长期以来，人们一直关注质膜钙泵（PMCAs），它与多种疾病有关，包括听力损失，神经退行性变和心脏病。我们在过去20年或更长时间的工作已经揭示了PMCA亚型的惊人复杂性，它们具有不同的功能特征、调节和细胞定位。新出现的证据表明，特定的PMCA不仅有助于设定基础细胞内Ca（2+）水平，还有助于局部Ca（2+）信号传导和矢量Ca（2+）转运。第二个主要的研究领域围绕钙传感器蛋白钙调素和一个神秘的钙调素样蛋白（CALML 3），这是与上皮分化。CALML 3的细胞靶点之一是非常规的运动蛋白肌球蛋白-10，这提出了关于CALML 3和肌球蛋白-10在正常细胞分化和癌症中的细胞粘附和迁移中的作用的新问题。
Cells are equipped with mechanisms to control tightly the influx, efflux and resting level of free calcium (Ca(2+)). Inappropriate Ca(2+) signaling and abnormal Ca(2+) levels are involved in many clinical disorders including heart disease, Alzheimer's disease and stroke. Ca(2+) also plays a major role in cell growth, differentiation and motility; disturbances in these processes underlie cell transformation and the progression of cancer. Accordingly, research in the Strehler laboratory is focused on a better understanding of the molecular "toolkit" needed to ensure proper Ca(2+) homeostasis in the cell, as well as on the mechanisms of localized Ca(2+) signaling. A long-term focus has been on the plasma membrane calcium pumps (PMCAs), which are linked to multiple disorders including hearing loss, neurodegeneration, and heart disease. Our work over the past 20 years or more has revealed a surprising complexity of PMCA isoforms with different functional characteristics, regulation, and cellular localization. Emerging evidence shows how specific PMCAs contribute not only to setting basal intracellular Ca(2+) levels, but also to local Ca(2+) signaling and vectorial Ca(2+) transport. A second major research area revolves around the calcium sensor protein calmodulin and an enigmatic calmodulin-like protein (CALML3) that is linked to epithelial differentiation. One of the cellular targets of CALML3 is the unconventional motor protein myosin-10, which raises new questions about the role of CALML3 and myosin-10 in cell adhesion and migration in normal cell differentiation and cancer.