The Rap1-cofilin-1 pathway coordinates actin reorganization and MTOC polarization at the B cell immune synapse
| Autor: | Jia C, Wang, Jeff Y-J, Lee, Sonja, Christian, May, Dang-Lawson, Caitlin, Pritchard, Spencer A, Freeman, Michael R, Gold |
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| Rok vydání: | 2016 |
| Předmět: |
Cofilin 1
Male B-Lymphocytes Immunological Synapses Cell Membrane Antigen-Presenting Cells Cell Polarity Dyneins Receptors Antigen B-Cell rap1 GTP-Binding Proteins Microtubules Models Biological Actins Cell Line Neoplasm Proteins Mice Inbred C57BL ras GTPase-Activating Proteins Animals Humans Female Microtubule-Associated Proteins Microtubule-Organizing Center Signal Transduction |
| Zdroj: | Journal of cell science. 130(6) |
| ISSN: | 1477-9137 |
| Popis: | B cells that bind antigens displayed on antigen-presenting cells (APCs) form an immune synapse, a polarized cellular structure that optimizes the dual functions of the B cell receptor (BCR), signal transduction and antigen internalization. Immune synapse formation involves polarization of the microtubule-organizing center (MTOC) towards the APC. We now show that BCR-induced MTOC polarization requires the Rap1 GTPase (which has two isoforms, Rap1a and Rap1b), an evolutionarily conserved regulator of cell polarity, as well as cofilin-1, an actin-severing protein that is regulated by Rap1. MTOC reorientation towards the antigen contact site correlated strongly with cofilin-1-dependent actin reorganization and cell spreading. We also show that BCR-induced MTOC polarization requires the dynein motor protein as well as IQGAP1, a scaffolding protein that can link the actin and microtubule cytoskeletons. At the periphery of the immune synapse, IQGAP1 associates closely with F-actin structures and with the microtubule plus-end-binding protein CLIP-170 (also known as CLIP1). Moreover, the accumulation of IQGAP1 at the antigen contact site depends on F-actin reorganization that is controlled by Rap1 and cofilin-1. Thus the Rap1-cofilin-1 pathway coordinates actin and microtubule organization at the immune synapse. |
| Databáze: | OpenAIRE |
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