Abstract：
The cellular functions are regulated by a complex interplay of diffuse and local signals. Studying the latter is challenging, but experimental work in cell physiology has led to recognize that understanding a cell\'s dynamics requires a deep comprehension of local fluctuations of cytosolic regulators. Macromolecular complexes are major determinants of local signaling. Multienzyme assemblies limit the diffusion restriction to reaction kinetics by direct exchange of metabolites. Likewise, close coupling of ion channels and transporters modulates the ion concentration around a channel mouth or transporter binding site. Extreme signal locality is brought about by conformational coupling between membrane proteins, as is typical of mechanotransduction. A paradigmatic case is integrin-mediated cell adhesion. Sensing the extracellular microenvironment and providing an appropriate response are essential in growth and development and have innumerable pathological implications. The process involves bidirectional signal transduction by complex supramolecular structures that link integrin receptors to ion channels and transporters, growth factor receptors, cytoskeletal elements, and other regulatory elements. The dynamics of such complexes are only beginning to be understood. A thoroughly studied example is the association between integrin receptors and the voltage-gated K+ channels Kv11.1. These channels are widely expressed in early embryos, where their physiological roles are poorly understood and apparently different from the shaping of action potential firing in the adult. Hints about these roles come from studies in cancer cells, where Kv11.1 is often overexpressed and appears to reassume functions it presumably exerts during embryogenesis, such as controlling cell proliferation/differentiation, apoptosis, and migration. Kv11.1 is implicated in these processes through its linking to integrin subunits, which in turn regulates channel expression. Specific cellular functions, such as proliferation and migration, appear to be modulated by distinct conformational states of the channel (e.g., open and closed), whose balance is affected by the link with integrin subunits.
摘要：
细胞功能受扩散和局部信号的复杂相互作用调节。研究后者是具有挑战性的，但是细胞生理学的实验工作已经使人们认识到，理解细胞的动力学需要对细胞溶质调节因子的局部波动有深刻的理解。大分子复合物是局部信号传导的主要决定因素。多酶组装体通过代谢物的直接交换将扩散限制限制为反应动力学。同样，离子通道和转运蛋白的紧密耦合调节通道口或转运蛋白结合位点周围的离子浓度。极端信号局部性是由膜蛋白之间的构象偶联引起的，这是典型的机械传导。典型的情况是整合素介导的细胞粘附。感知细胞外微环境并提供适当的反应在生长和发育中至关重要，并且具有无数的病理意义。该过程涉及通过将整联蛋白受体与离子通道和转运体连接的复杂超分子结构进行双向信号转导。生长因子受体，细胞骨架元素，和其他监管要素。这种复合物的动力学才刚刚开始被理解。一个经过深入研究的例子是整合素受体与电压门控K通道Kv11.1之间的关联。这些通道在早期胚胎中广泛表达，对它们的生理作用知之甚少，显然与成年人动作电位放电的形成不同。关于这些作用的提示来自癌细胞的研究，其中Kv11.1通常是过表达的，并且似乎重新假定了它在胚胎发生过程中可能发挥的功能，如控制细胞增殖/分化，凋亡，和移民。Kv11.1通过与整联蛋白亚基的连接参与了这些过程，进而调节通道表达。特定的细胞功能，如扩散和迁移，似乎是由通道的不同构象状态调制的(例如，打开和关闭)，其平衡受到与整合素亚基的联系的影响。
