*MOE Key Laboratory of Protein Science, School of Life Sciences, and State Key Joint Laboratory of Environment Simulation and Pollution Control, School of Environment, Tsinghua University, Beijing, China; Collaborative Innovation Center for Infectious Diseases, Hangzhou, China; Department of Rheumatology and Immunology, Clinical Immunology Center, Peking University People's Hospital, Beijing, China; Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China; and Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, China.
*MOE Key Laboratory of Protein Science, School of Life Sciences, and State Key Joint Laboratory of Environment Simulation and Pollution Control, School of Environment, Tsinghua University, Beijing, China; Collaborative Innovation Center for Infectious Diseases, Hangzhou, China; Department of Rheumatology and Immunology, Clinical Immunology Center, Peking University People's Hospital, Beijing, China; Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China; and Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, China
J Leukoc Biol. 2015 Aug;98(2):223-34. doi: 10.1189/jlb.2A0614-287RR. Epub 2015 May 15.
Sphingolipid- and cholesterol-rich lipid raft microdomains are important in the initiation of BCR signaling. Although it is known that lipid rafts promote the coclustering of BCR and Lyn kinase microclusters within the B cell IS, the molecular mechanism of the recruitment of lipid rafts into the B cell IS is not understood completely. Here, we report that the synaptic recruitment of lipid rafts is dependent on the cytoskeleton-remodeling proteins, RhoA and Vav. Such an event is also efficiently regulated by motor proteins, myosin IIA and dynein. Further evidence suggests the synaptic recruitment of lipid rafts is, by principle, an event triggered by BCR signaling molecules and second messenger molecules. BCR-activating coreceptor CD19 potently enhances such an event depending on its cytoplasmic Tyr421 and Tyr482 residues. The enhancing function of the CD19-PI3K module in synaptic recruitment of lipid rafts is also confirmed in human peripheral blood B cells. Thus, these results improve our understanding of the molecular mechanism of the recruitment of lipid raft microdomains in B cell IS.
鞘脂和胆固醇丰富的脂筏微区在 BCR 信号的起始中很重要。虽然已知脂筏促进 B 细胞 IS 内 BCR 和 Lyn 激酶微簇的共聚类，但脂筏募集到 B 细胞 IS 的分子机制尚不完全清楚。在这里，我们报告说，脂筏的突触募集依赖于细胞骨架重塑蛋白 RhoA 和 Vav。这种事件也可以被肌球蛋白 IIA 和动力蛋白等运动蛋白有效地调节。进一步的证据表明，脂筏的突触募集原则上是由 BCR 信号分子和第二信使分子触发的事件。BCR 激活的共受体 CD19 通过其细胞质 Tyr421 和 Tyr482 残基强烈增强这种事件。CD19-PI3K 模块在脂筏突触募集中的增强功能也在人外周血 B 细胞中得到证实。因此，这些结果提高了我们对 B 细胞 IS 中脂筏微区募集的分子机制的理解。
