Ecm29-Dependent Proteasome Localization Regulates Cytoskeleton Remodeling at the Immune Synapse

• DOI: 10.3389/fcell.2021.650817
• Publication Date: 2021-05-13T06:05:57Z
• Authors: Jorge Ibañez-Vega; Felipe Del Valle; Juan José Sáez; Fanny Guzman; Jheimmy Diaz; Andrea Soza; María Isabel Yuseff
• Keywords: 0301 basic medicine; B cell; 570; actin cytoskeleton; Ecm29; QH301-705.5; immune synapse; 610; microtubules; Cell and Developmental Biology; 03 medical and health sciences; proteasome; lysosomes; 03 Salud y bienestar; 03 Good Health and Well-being; Biology (General)

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.