Department of Immunology, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, Ohio 44195, United States.
J Proteome Res. 2011 Sep 2;10(9):3983-92. doi: 10.1021/pr200577d. Epub 2011 Jul 28.
The molecular regulation of recruitment and assembly of signalosomes near the B cell receptor (BCR) is poorly understood. We have previously demonstrated a role for the ERM family protein ezrin in regulating antigen-dependent lipid raft coalescence in B cells. In this study, we addressed the possibility that ezrin may collaborate with other adaptor proteins to regulate signalosome dynamics at the membrane. Using mass spectrometry-based proteomics analysis, we identified Myo18aα as a novel binding partner of ezrin. Myo18aα is an attractive candidate as it has several protein-protein interaction domains and an intrinsic motor activity. The expression of Myo18aα varied during B cell development in the bone marrow and in mature B cell subsets suggesting functional differences. Interestingly, BCR stimulation increased the association between ezrin and Myo18aα, and induced co-segregation of Myo18aα with the BCR and phosphotyrosine-containing proteins. Our data raise an intriguing possibility that the Myo18aα/ezrin complex may facilitate BCR-mediated signaling by recruiting signaling proteins that are in close proximity of the antigen receptor. Our study is not only significant with respect to understanding the molecular regulation of BCR signaling but also provides a broader basis for understanding the mechanism of action of ezrin in other cellular systems.
信号转导小体在 B 细胞受体 (BCR) 附近的募集和组装的分子调控机制还不太清楚。我们之前已经证明 ERM 家族蛋白 ezrin 在调节 B 细胞中抗原依赖性脂筏聚集中起作用。在这项研究中，我们探讨了 ezrin 是否可能与其他衔接蛋白合作来调节膜上信号转导小体的动态。通过基于质谱的蛋白质组学分析，我们鉴定出 Myo18aα 是 ezrin 的一个新的结合伴侣。Myo18aα 是一个很有吸引力的候选蛋白，因为它具有几个蛋白质-蛋白质相互作用域和内在的分子马达活性。Myo18aα 的表达在骨髓中的 B 细胞发育和成熟 B 细胞亚群中发生变化，表明存在功能差异。有趣的是，BCR 刺激增加了 ezrin 和 Myo18aα 之间的关联，并诱导 Myo18aα 与 BCR 和含磷酸酪氨酸的蛋白质共同聚集。我们的数据提出了一个有趣的可能性，即 Myo18aα/ezrin 复合物可能通过招募与抗原受体紧密相邻的信号蛋白来促进 BCR 介导的信号转导。我们的研究不仅对理解 BCR 信号转导的分子调控具有重要意义，而且为理解 ezrin 在其他细胞系统中的作用机制提供了更广泛的基础。
