title: The synaptic recruitment of lipid rafts is dependent on CD19-PI3K module and cytoskeleton remodeling molecules.
abstract: 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.
authors.affiliation: *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.
authors.forename: Liling
authors.initials: L
authors.lastname: Xu
authors.affiliation: *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.
authors.forename: Arturs
authors.initials: A
authors.lastname: Auzins
authors.affiliation: *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.
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Sun
authors.affiliation: *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.
authors.forename: Yinsheng
authors.initials: Y
authors.lastname: Xu
authors.affiliation: *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.
authors.forename: Fiona
authors.initials: F
authors.lastname: Harnischfeger
authors.affiliation: *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.
authors.forename: Yun
authors.initials: Y
authors.lastname: Lu
authors.affiliation: *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.
authors.forename: Zhanguo
authors.initials: Z
authors.lastname: Li
authors.affiliation: *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 liuwanli@biomed.tsinghua.edu.cn chenyh@tsinghua.edu.cn wenjzheng@gmail.com.
authors.forename: Ying-Hua
authors.initials: YH
authors.lastname: Chen
authors.affiliation: *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.
authors.forename: Wenjie
authors.initials: W
authors.lastname: Zheng
authors.affiliation: *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 liuwanli@biomed.tsinghua.edu.cn chenyh@tsinghua.edu.cn wenjzheng@gmail.com.
authors.forename: Wanli
authors.initials: W
authors.lastname: Liu
mesh_terms: D008841:Actin Cytoskeleton / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D018941:Antigens, CD19 / Q000235:genetics* / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D001692:Biological Transport; D002460:Cell Line; D058543:Class Ia Phosphatidylinositol 3-Kinase / Q000235:genetics* / Q000276:immunology; D004398:Dyneins / Q000235:genetics / Q000276:immunology; D005786:Gene Expression Regulation; D006801:Humans; D054992:Immunological Synapses / Q000737:chemistry / Q000378:metabolism*; D008213:Lymphocyte Activation; D021962:Membrane Microdomains / Q000276:immunology / Q000378:metabolism*; D061251:Primary Cell Culture; D051567:Proto-Oncogene Proteins c-vav / Q000235:genetics / Q000276:immunology; D011947:Receptors, Antigen, B-Cell / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction; D020742:rhoA GTP-Binding Protein / Q000235:genetics / Q000276:immunology; D019061:src-Family Kinases / Q000235:genetics / Q000276:immunology
chemical_list: D018941:Antigens, CD19; D051567:Proto-Oncogene Proteins c-vav; D011947:Receptors, Antigen, B-Cell; C066737:RHOA protein, human; D058543:Class Ia Phosphatidylinositol 3-Kinase; C060902:lyn protein-tyrosine kinase; D019061:src-Family Kinases; D004398:Dyneins; D020742:rhoA GTP-Binding Protein
keywords: B cell activation; BCR; immunological synapse