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

Frontiers in Cell and Developmental Biology

Andrea Soza²  María Isabel Yuseff³  Juan José Sáez³  Jheimmy Diaz³  Jorge Ibañez-Vega³  Felipe Del Valle³  Fanny Guzman⁴ 

[1] Centro de Biología Celular y Biomedicina, Facultad de Medicina y Ciencia, Universidad San Sebastián, Santiago, Chile;Centro de Envejecimiento y Regeneración (CARE), Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile;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;

关键词: proteasome;    actin cytoskeleton;    Ecm29;    immune synapse;    lysosomes;    microtubules;   

DOI  :  10.3389/fcell.2021.650817

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown