Lipid rafts unite signaling cascades with clathrin to regulate BCR internalization.
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.
Stoddart
Angela
A
The G.W. Hooper Foundation, Department of Microbiology and Immunology, University of California, San Francisco 94143, USA.
Dykstra
Michelle L
ML
Brown
Bruce K
BK
Song
Wenxia
W
Pierce
Susan K
SK
Brodsky
Frances M
FM
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
D002966:Clathrin; D008024:Ligands; D011947:Receptors, Antigen, B-Cell; D019061:src-Family Kinases