title: Lipid rafts unite signaling cascades with clathrin to regulate BCR internalization.
abstract: A major function of the B cell is the internalization of antigen through the BCR for processing and presentation to T cells. While there is evidence suggesting that lipid raft signaling may regulate internalization, the molecular machinery coordinating these two processes remains to be defined. Here we present a link between the B cell signaling and internalization machinery and show that Src-family kinase activity is required for inducible clathrin heavy chain phosphorylation, BCR colocalization with clathrin, and regulated internalization. An analysis of different B cell lines shows that BCR uptake occurs only when clathrin is associated with rafts and is tyrosine phosphorylated following BCR crosslinking. We therefore propose that lipid rafts spatially organize signaling cascades with clathrin to regulate BCR internalization.
authors.affiliation: The G.W. Hooper Foundation, Department of Microbiology and Immunology, University of California, San Francisco 94143, USA.
authors.forename: Angela
authors.initials: A
authors.lastname: Stoddart
authors.forename: Michelle L
authors.initials: ML
authors.lastname: Dykstra
authors.forename: Bruce K
authors.initials: BK
authors.lastname: Brown
authors.forename: Wenxia
authors.initials: W
authors.lastname: Song
authors.forename: Susan K
authors.initials: SK
authors.lastname: Pierce
authors.forename: Frances M
authors.initials: FM
authors.lastname: Brodsky
mesh_terms: D017951:Antigen Presentation; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D001693:Biological Transport, Active; D002460:Cell Line; D002966:Clathrin / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008024:Ligands; D021962:Membrane Microdomains / Q000737:chemistry / Q000378:metabolism*; D010766:Phosphorylation; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism*; D015398:Signal Transduction; D019061:src-Family Kinases / Q000378:metabolism
chemical_list: D002966:Clathrin; D008024:Ligands; D011947:Receptors, Antigen, B-Cell; D019061:src-Family Kinases