Ibañez-Vega Jorge, Del Valle Felipe, Sáez Juan José, Guzman Fanny, Diaz Jheimmy, Soza Andrea, Yuseff María Isabel
Departamento de Biología Celular y Molecular, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile.
Núcleo Biotecnología Curauma, Pontificia Universidad Católica de Valparaíso, Valparaíso, Chile.
Front Cell Dev Biol. 2021 May 13;9:650817. doi: 10.3389/fcell.2021.650817. eCollection 2021.
The formation of an immune synapse (IS) enables B cells to capture membrane-tethered antigens, where cortical actin cytoskeleton remodeling regulates cell spreading and depletion of F-actin at the centrosome promotes the recruitment of lysosomes to facilitate antigen extraction. How B cells regulate both pools of actin, remains poorly understood. We report here that decreased F-actin at the centrosome and IS relies on the distribution of the proteasome, regulated by Ecm29. Silencing Ecm29 decreases the proteasome pool associated to the centrosome of B cells and shifts its accumulation to the cell cortex and IS. Accordingly, Ecm29-silenced B cells display increased F-actin at the centrosome, impaired centrosome and lysosome repositioning to the IS and defective antigen extraction and presentation. Ecm29-silenced B cells, which accumulate higher levels of proteasome at the cell cortex, display decreased actin retrograde flow in lamellipodia and enhanced spreading responses. Our findings support a model where B the asymmetric distribution of the proteasome, mediated by Ecm29, coordinates actin dynamics at the centrosome and the IS, promoting lysosome recruitment and cell spreading.
免疫突触（IS）的形成使B细胞能够捕获膜结合抗原，其中皮质肌动蛋白细胞骨架重塑调节细胞铺展，而中心体处F-肌动蛋白的消耗促进溶酶体的募集以利于抗原提取。B细胞如何调节这两种肌动蛋白池仍知之甚少。我们在此报告，中心体和免疫突触处F-肌动蛋白的减少依赖于由Ecm29调节的蛋白酶体分布。沉默Ecm29会减少与B细胞中心体相关的蛋白酶体池，并使其积累转移到细胞皮质和免疫突触。相应地，Ecm29沉默的B细胞在中心体处显示F-肌动蛋白增加，中心体和溶酶体向免疫突触的重新定位受损，抗原提取和呈递存在缺陷。在细胞皮质积累更高水平蛋白酶体的Ecm29沉默B细胞，在片足中显示肌动蛋白逆行流减少，铺展反应增强。我们的研究结果支持一种模型，即由Ecm29介导的蛋白酶体不对称分布协调中心体和免疫突触处的肌动蛋白动力学，促进溶酶体募集和细胞铺展。
