Department of Cytobiochemistry, Faculty of Biotechnology, University of Wrocław, ul. F. Joliot-Curie 14a, 50-383 Wrocław, Poland.
Department of Biotransformation, Faculty of Biotechnology, University of Wrocław, ul. F. Joliot-Curie 14a, 50-383 Wrocław, Poland.
Cells. 2022 Jan 18;11(3):311. doi: 10.3390/cells11030311.
MPP1 (membrane palmitoylated protein 1) belongs to the MAGUK (membrane-associated guanylate kinase homologs) scaffolding protein family. These proteins organize molecules into complexes, thereby maintaining the structural heterogeneity of the plasma membrane (PM). Our previous results indicated that direct, high-affinity interactions between MPP1 and flotillins (raft marker proteins) display dominant PM-modulating capacity in erythroid cells. In this study, with high-resolution structured illuminated imaging, we investigated how these complexes are organized within erythroid cells on the nanometer scale. Furthermore, using other spectroscopic techniques, namely fluorescence recovery after photobleaching (FRAP) and spot-variation fluorescence correlation spectroscopy (svFCS), we revealed that MPP1 acts as a key raft-capturing molecule, regulating temporal immobilization of flotillin-based nanoclusters, and controls local concentration and confinement of sphingomyelin and Thy-1 in raft nanodomains. Our data enabled us to uncover molecular principles governing the key involvement of MPP1-flotillin complexes in the dynamic nanoscale organization of PM of erythroid cells.
MPP1（膜棕榈酰化蛋白 1）属于 MAGUK（膜相关鸟苷酸激酶同源物）支架蛋白家族。这些蛋白质将分子组织成复合物，从而维持质膜（PM）的结构异质性。我们之前的结果表明，MPP1 与 flotillins（筏标记蛋白）之间的直接、高亲和力相互作用在红细胞中显示出主导的 PM 调节能力。在这项研究中，我们使用高分辨率结构照明成像技术，在纳米尺度上研究了这些复合物在红细胞内是如何组织的。此外，我们还使用其他光谱技术，即光漂白后荧光恢复（FRAP）和斑点变化荧光相关光谱（svFCS），揭示了 MPP1 作为一种关键的筏捕获分子，调节 flotillin 基纳米簇的时间固定化，并控制鞘磷脂和 Thy-1 在筏纳米域中的局部浓度和限制。我们的数据使我们能够揭示控制 MPP1-flotillin 复合物在红细胞质膜动态纳米尺度组织中关键参与的分子原理。
