Program in Biophysics, University of Michigan, Ann Arbor, MI, USA.
Department of Biochemistry & Cellular and Molecular Biology, University of Tennessee Knoxville, Knoxville, TN, USA.
Nat Chem Biol. 2023 Jun;19(6):750-758. doi: 10.1038/s41589-023-01268-8. Epub 2023 Mar 30.
Plasma membrane heterogeneity has been tied to a litany of cellular functions and is often explained by analogy to membrane phase separation; however, models based on phase separation alone fall short of describing the rich organization available within cell membranes. Here we present comprehensive experimental evidence motivating an updated model of plasma membrane heterogeneity in which membrane domains assemble in response to protein scaffolds. Quantitative super-resolution nanoscopy measurements in live B lymphocytes detect membrane domains that emerge upon clustering B cell receptors (BCRs). These domains enrich and retain membrane proteins based on their preference for the liquid-ordered phase. Unlike phase-separated membranes that consist of binary phases with defined compositions, membrane composition at BCR clusters is modulated through the protein constituents in clusters and the composition of the membrane overall. This tunable domain structure is detected through the variable sorting of membrane probes and impacts the magnitude of BCR activation.
质膜异质性与许多细胞功能有关，通常可以通过类比膜相分离来解释；然而，仅基于相分离的模型不足以描述细胞内丰富的膜组织。在这里，我们提供了全面的实验证据，支持一个更新的质膜异质性模型，该模型中膜域的组装是响应于蛋白质支架的。在活 B 淋巴细胞中进行的定量超分辨率纳米显微镜测量检测到了 B 细胞受体 (BCR) 聚类时出现的膜域。这些域根据其对液相的偏好来富集和保留膜蛋白。与由二元相组成且组成明确的相分离膜不同，BCR 簇中的膜组成通过簇中的蛋白质成分和膜的整体组成来调节。这种可调域结构通过膜探针的可变分类检测到，并影响 BCR 激活的幅度。
