Nanoscale Organization of the OHC Lateral Wall

描述（由申请人提供）：本申请的长期目标是确定在耳蜗外毛细胞（OHC）中发现的膜蛋白（在这种情况下为普雷斯廷）如何能够使电压诱导的细胞变形。为此，我们将研究蛋白质-蛋白质，蛋白质-脂质和膜-细胞骨架的相互作用。为了了解普雷斯廷如何影响膜的变形，我们将使用一种称为荧光偏振显微镜（FPM）的光学技术来研究膜分子在微扰下的行为。我们还将研究如何分子组成的细胞骨架下变形行为使用相同的技术。最后，尽管普雷斯廷被广泛认为是OHC中的膜运动蛋白，但对其作用机制知之甚少。我们假设，普雷斯廷可能是相互作用的本身或其他膜蛋白，诱导长度的变化，并建议使用荧光共振能量转移来量化的相互作用的程度。这些研究的结果将进一步阐明普雷斯廷在电运动中的作用及其作为膜蛋白的功能。

DESCRIPTION (provided by applicant): The long term goal of this application is to determine how a membrane protein, in this case prestin, found in cochlear outer hair cells (OHCs), can enable voltage-induced cell deformation. To this end, we will study protein-protein, protein-lipid, and membrane-cytoskeleton interactions. To understand how prestin affects membrane deformation, we will study the behavior of membrane molecules under perturbation using an optical technique called fluorescence polarization microscopy (FPM). We will also study how molecules that comprise the cytoskeleton behave under deformation using the same technique. Lastly, though prestin is widely accepted as the membrane motor protein in OHCs, little is known about its mechanism of action. We hypothesize that prestin may be interacting with itself or other membrane proteins to induce length changes and propose to use fluorescence resonance energy transfer to quantify the degree of interaction. The results from each of these proposed studies will further elucidate prestin's role in electromotility and its function as a membrane protein.