Institute of Cell Dynamics and Imaging, and Cells-in-Motion Interfaculty Center (CiMIC), University of Münster, Münster, Germany.
Institute for Medical Physics and Biophysics, and Cells-in-Motion Interfaculty Center (CiMIC), Münster, Germany.
EMBO Rep. 2023 Dec 6;24(12):e57232. doi: 10.15252/embr.202357232. Epub 2023 Oct 30.
The topography of biological membranes is critical for formation of protein and lipid microdomains. One prominent example in the yeast plasma membrane (PM) are BAR domain-induced PM furrows. Here we report a novel function for the Sur7 family of tetraspanner proteins in the regulation of local PM topography. Combining TIRF imaging, STED nanoscopy, freeze-fracture EM and membrane simulations we find that Sur7 tetraspanners form multimeric strands at the edges of PM furrows, where they modulate forces exerted by BAR domain proteins at the furrow base. Loss of Sur7 tetraspanners or Sur7 displacement due to altered PIP2 homeostasis leads to increased PM invagination and a distinct form of membrane tubulation. Physiological defects associated with PM tubulation are rescued by synthetic anchoring of Sur7 to furrows. Our findings suggest a key role for tetraspanner proteins in sculpting local membrane domains. The maintenance of stable PM furrows depends on a balance between negative curvature at the base which is generated by BAR domains and positive curvature at the furrows' edges which is stabilized by strands of Sur7 tetraspanners.
生物膜的拓扑结构对于蛋白质和脂质微区的形成至关重要。在酵母质膜（PM）中，一个突出的例子是 BAR 结构域诱导的 PM 皱襞。在这里，我们报告了 tetraspanner 蛋白 Sur7 家族在调节局部 PM 拓扑结构中的新功能。通过 TIRF 成像、STED 纳米显微镜、冷冻断裂 EM 和膜模拟，我们发现 Sur7 tetraspanner 在 PM 皱襞的边缘形成多聚体链，在那里它们调节 BAR 结构域蛋白在皱襞底部施加的力。Sur7 tetraspanner 的缺失或由于 PIP2 动态平衡改变导致的 Sur7 易位会导致 PM 内陷增加和膜小管的独特形式。通过将 Sur7 合成锚定到皱襞上，可以挽救与 PM 小管化相关的生理缺陷。我们的发现表明 tetraspanner 蛋白在塑造局部膜域方面起着关键作用。稳定的 PM 皱襞的维持取决于基底处负曲率和皱襞边缘处正曲率之间的平衡，基底处的负曲率由 BAR 结构域产生，皱襞边缘处的正曲率由 Sur7 tetraspanner 链稳定。
