The actin cytoskeleton is required for the trafficking of the B cell antigen receptor to the late endosomes.
The B cell antigen receptor (BCR) plays two central roles in B cell activation: to internalize antigens for processing and presentation, and to initiate signal transduction cascades that both promote B cells to enter the cell cycle and facilitate antigen processing by accelerating antigen transport. An early event in B cell activation is the association of BCR with the actin cytoskeleton, and an increase in cellular F-actin. Current evidence indicates that the organization of actin filaments changes in response to BCR-signaling, making actin filaments good candidates for regulation of BCR-antigen targeting. Here, we have analyzed the role of actin filaments in BCR-mediated antigen transport, using actin filament-disrupting reagents, cytochalasin D and latrunculin B, and an actin filament-stabilizing reagent, jasplakinolide. Perturbing actin filaments, either by disrupting or stabilizing them, blocked the movement of BCR from the plasma membrane to late endosomes/lysosomes. Cytochalasin D-treatment dramatically reduced the rate of internalization of BCR, and blocked the movement of the BCR from early endosomes to late endosomes/lysosomes, without affecting BCR-signaling. Thus, BCR-trafficking requires functional actin filaments for both internalization and movement to late endosomes/lysosomes, defining critical control points in BCR-antigen targeting.
Brown
B K
BK
Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, MD 20742, USA.
Song
W
W
D000199:Actins / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D003432:Cross-Linking Reagents / Q000494:pharmacology; D015638:Cytochalasin D / Q000494:pharmacology; D003599:Cytoskeleton / Q000378:metabolism*; D047630:Depsipeptides; D004305:Dose-Response Relationship, Drug; D011992:Endosomes / Q000378:metabolism*; D006801:Humans; D006825:Hybridomas / Q000378:metabolism; D008213:Lymphocyte Activation; D008247:Lysosomes / Q000378:metabolism; D051379:Mice; D008854:Microscopy, Electron; D008856:Microscopy, Fluorescence; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000494:pharmacology; D010766:Phosphorylation; D021381:Protein Transport; D051381:Rats; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism*; D015398:Signal Transduction; D013844:Thiazoles / Q000494:pharmacology; D053778:Thiazolidines; D013997:Time Factors; D014443:Tyrosine / Q000378:metabolism
D000199:Actins; D000970:Antineoplastic Agents; D019086:Bridged Bicyclo Compounds, Heterocyclic; D003432:Cross-Linking Reagents; D047630:Depsipeptides; D019384:Nucleic Acid Synthesis Inhibitors; D010456:Peptides, Cyclic; D011947:Receptors, Antigen, B-Cell; D013844:Thiazoles; D053778:Thiazolidines; C057531:jasplakinolide; D015638:Cytochalasin D; D014443:Tyrosine; C037068:latrunculin B