Microfilament assembly is involved in B-cell apoptosis.
Crosslinking of the B-cell antigen receptor (BCR) initiates a chain of reactions which culminate in a number of biologic responses, including entry into the cell cycle or cell death. The signals and processes which lead to cell death are slowly being unraveled. Based on the dramatic changes in cell shape which occur during progression of the apoptotic response, activation of cytoskeletal assembly may be critical as this appears to be essential to the mitogenic response. In this study, we demonstrate that crosslinking of the human BCR with anti-IgM antibodies results in the rapid assembly of actin. Our data also suggest that this conversion of G- to F-actin may be a prerequisite for the apoptosis response, as prevention of this conversion by botulinum C2 toxin or cytochalasin D results in rescue of the cells from apoptosis. Prevention of tyrosine kinase activation, disruption of microfilament assembly, and rescue of B lymphocytes from apoptosis imply that tyrosine phosphorylation is needed for both microfilament assembly and apoptosis. In each instance where microfilament assembly is inhibited, anti-IgM-induced activation of the protease CPP32 (caspase) is also inhibited. Taken together, these results suggest that the microfilament system is actively involved in delivering signals for apoptosis.
Melamed
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Department of Pediatrics, National Jewish Medical and Research Center, Denver, Colorado, 80206, USA.
Gelfand
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EW
D008841:Actin Cytoskeleton / Q000502:physiology*; D000199:Actins / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D017209:Apoptosis; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D001905:Botulinum Toxins / Q000494:pharmacology; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D015638:Cytochalasin D / Q000494:pharmacology; D003599:Cytoskeleton / Q000502:physiology; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D007075:Immunoglobulin M / Q000276:immunology; D011108:Polymers; D015398:Signal Transduction; D020032:Tyrphostins / Q000494:pharmacology
D000199:Actins; D004791:Enzyme Inhibitors; D007075:Immunoglobulin M; D011108:Polymers; D020032:Tyrphostins; D015638:Cytochalasin D; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; D001905:Botulinum Toxins; C096324:botulinum toxin type C