The Wdr1-LIMK-Cofilin Axis Controls B Cell Antigen Receptor-Induced Actin Remodeling and Signaling at the Immune Synapse
| Autor: | Connor Keane, May Dang-Lawson, Kate Choi, Michael R. Gold, Faith Cheung, Madison Bolger-Munro, Nikola Deretic, Yi Tian Liu |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
macromolecular substances cofilin Immunological synapse Cell and Developmental Biology 03 medical and health sciences cell spreading 0302 clinical medicine WDR1 (AIP1) medicine lcsh:QH301-705.5 B cell Actin Original Research LIM domain kinase Chemistry immune synapse breakpoint cluster region Actin remodeling Cell Biology Cofilin B cell receptor (BCR) Actin cytoskeleton Actin filament depolymerization Cell biology 030104 developmental biology medicine.anatomical_structure lcsh:Biology (General) actin 030217 neurology & neurosurgery Developmental Biology |
| Zdroj: | Frontiers in Cell and Developmental Biology, Vol 9 (2021) Frontiers in Cell and Developmental Biology |
| ISSN: | 2296-634X |
| Popis: | When B cells encounter membrane-bound antigens, the formation and coalescence of B cell antigen receptor (BCR) microclusters amplifies BCR signaling. The ability of B cells to probe the surface of antigen-presenting cells (APCs) and respond to APC-bound antigens requires remodeling of the actin cytoskeleton. Initial BCR signaling stimulates actin-related protein (Arp) 2/3 complex-dependent actin polymerization, which drives B cell spreading as well as the centripetal movement and coalescence of BCR microclusters at the B cell-APC synapse. Sustained actin polymerization depends on concomitant actin filament depolymerization, which enables the recycling of actin monomers and Arp2/3 complexes. Cofilin-mediated severing of actin filaments is a rate-limiting step in the morphological changes that occur during immune synapse formation. Hence, regulators of cofilin activity such as WD repeat-containing protein 1 (Wdr1), LIM domain kinase (LIMK), and coactosin-like 1 (Cotl1) may also be essential for actin-dependent processes in B cells. Wdr1 enhances cofilin-mediated actin disassembly. Conversely, Cotl1 competes with cofilin for binding to actin and LIMK phosphorylates cofilin and prevents it from binding to actin filaments. We now show that Wdr1 and LIMK have distinct roles in BCR-induced assembly of the peripheral actin structures that drive B cell spreading, and that cofilin, Wdr1, and LIMK all contribute to the actin-dependent amplification of BCR signaling at the immune synapse. Depleting Cotl1 had no effect on these processes. Thus, the Wdr1-LIMK-cofilin axis is critical for BCR-induced actin remodeling and for B cell responses to APC-bound antigens. |
| Databáze: | OpenAIRE |
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