--- res: bibo_abstract: - 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.@eng bibo_authorlist: - foaf_Person: foaf_givenName: Madison foaf_name: Bolger-Munro, Madison foaf_surname: Bolger-Munro foaf_workInfoHomepage: http://www.librecat.org/personId=516F03FA-93A3-11EA-A7C5-D6BE3DDC885E orcid: 0000-0002-8176-4824 - foaf_Person: foaf_givenName: Kate foaf_name: Choi, Kate foaf_surname: Choi - foaf_Person: foaf_givenName: Faith foaf_name: Cheung, Faith foaf_surname: Cheung - foaf_Person: foaf_givenName: Yi Tian foaf_name: Liu, Yi Tian foaf_surname: Liu - foaf_Person: foaf_givenName: May foaf_name: Dang-Lawson, May foaf_surname: Dang-Lawson - foaf_Person: foaf_givenName: Nikola foaf_name: Deretic, Nikola foaf_surname: Deretic - foaf_Person: foaf_givenName: Connor foaf_name: Keane, Connor foaf_surname: Keane - foaf_Person: foaf_givenName: Michael R. foaf_name: Gold, Michael R. foaf_surname: Gold bibo_doi: 10.3389/fcell.2021.649433 bibo_volume: 9 dct_date: 2021^xs_gYear dct_identifier: - UT:000644419500001 dct_isPartOf: - http://id.crossref.org/issn/2296-634X dct_language: eng dct_publisher: Frontiers Media@ dct_subject: - B cell - actin - immune synapse - cell spreading - cofilin - WDR1 (AIP1) - LIM domain kinase - B cell receptor (BCR) dct_title: The Wdr1-LIMK-Cofilin axis controls B cell antigen receptor-induced actin remodeling and signaling at the immune synapse@ fabio_hasPubmedId: '33928084' ...