Cooperative unfolding of distinctive mechanoreceptor domains transduces force into signals

作者：Ju Lining; Chen Yunfeng; Xue Lingzhou; Du Xiaoping; Zhu Cheng^*

来源：eLife, 2016, 5: e15447.

DOI：10.7554/eLife.15447

How cells sense their mechanical environment and transduce forces into biochemical signals is a crucial yet unresolved question in mechanobiology. Platelets use receptor glycoprotein Ib (GPIb), specifically its alpha subunit (GPIb alpha), to signal as they tether and translocate on von Willebrand factor (VWF) of injured arterial surfaces against blood flow. Force slows VWF-GPIb alpha dissociation (catch bond) and unfolds the GPIb alpha leucine-rich repeat domain (LRRD) and juxtamembrane mechanosensitive domain (MSD). How these mechanical processes trigger biochemical signals remains unknown. Here we analyze these extracellular events and the resulting intracellular Ca2+ on a single platelet in real time, revealing that LRRD unfolding intensifies the Ca2+ signal analogously whereas MSD unfolding determines the Ca2+ type digitally. The >30nm macroglycopeptide separating the two domains transmits VWF-GPIb alpha bond lifetime prolonged by LRRD unfolding to enhance MSD unfolding cooperatively at an optimal force, which may serve as a design principle for a generic mechanosensory machine.

• 出版日期2016-7-19