Hilton Jacob K, Rath Parthasarathi, Helsell Cole V M, Beckstein Oliver, Van Horn Wade D
†Center for Personalized Diagnostics, Magnetic Resonance Research Center, and Department of Chemistry and Biochemistry, Arizona State University, 551 East University Drive, PSG-106, Tempe, Arizona 85287, United States.
‡Center for Biological Physics and Department of Physics, Arizona State University, 550 East Tyler Mall, Tempe, Arizona 85287, United States.
Biochemistry. 2015 Apr 21;54(15):2401-13. doi: 10.1021/acs.biochem.5b00071. Epub 2015 Apr 3.
Transient receptor potential (TRP) ion channels are eukaryotic polymodal sensors that function as molecular cellular signal integrators. TRP family members sense and are modulated by a wide array of inputs, including temperature, pressure, pH, voltage, chemicals, lipids, and other proteins. These inputs induce signal transduction events mediated by nonselective cation passage through TRP channels. In this review, we focus on the thermosensitive TRP channels and highlight the emerging view that these channels play a variety of significant roles in physiology and pathophysiology in addition to sensory biology. We attempt to use this viewpoint as a framework to understand the complexity and controversy of TRP channel modulation and ultimately suggest that the complex functional behavior arises inherently because this class of protein is exquisitely sensitive to many diverse and distinct signal inputs. To illustrate this idea, we primarily focus on TRP channel thermosensing. We also offer a structural, biochemical, biophysical, and computational perspective that may help to bring more coherence and consensus in understanding the function of this important class of proteins.
瞬时受体电位（TRP）离子通道是真核生物的多模态传感器，作为分子细胞信号整合器发挥作用。TRP家族成员可感知并受到多种输入的调节，包括温度、压力、pH值、电压、化学物质、脂质和其他蛋白质。这些输入会引发由非选择性阳离子通过TRP通道介导的信号转导事件。在本综述中，我们聚焦于热敏TRP通道，并强调一种新出现的观点，即除了感觉生物学外，这些通道在生理学和病理生理学中也发挥着多种重要作用。我们试图以此观点为框架来理解TRP通道调节的复杂性和争议性，并最终表明这种复杂的功能行为本质上是由于这类蛋白质对许多不同且独特的信号输入极为敏感而产生的。为了阐明这一观点，我们主要聚焦于TRP通道的热敏性。我们还提供了一个结构、生化、生物物理和计算方面的视角，这可能有助于在理解这类重要蛋白质的功能时带来更多的连贯性和共识。
