B cells extract antigens using Arp2/3-generated actin foci interspersed with linear filaments

Roper, Sophie Isabel; Wasim, Laabiah; Malinova, Dessislava; Way, Michael; Cox, Susan; Tolar, Pavel

doi:10.1101/792481

Cited by 2 publications

(2 citation statements)

References 33 publications

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“…Interestingly, Vti1b was found also to colocalise with lysosomes and F-actin foci at the IS. It has been proposed that endocytosis and exocytosis occur at these actin foci (Carisey et al, 2018;Roper et al, 2019;Calvo and Izquierdo, 2021), raising a hypothesis that Vti1b could play a role in antigen extraction at these structures.…”

Section: Discussionmentioning

confidence: 99%

The SNARE protein Vti1b is recruited to the sites of BCR activation but is redundant for antigen internalisation, processing and presentation

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Tejeda-González

Cunha

et al. 2022

Front. Cell Dev. Biol.

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In order to fulfil the special requirements of antigen-specific activation and communication with other immune cells, B lymphocytes require finely regulated endosomal vesicle trafficking. How the endosomal machinery is regulated in B cells remains largely unexplored. In our previous proximity proteomic screen, we identified the SNARE protein Vti1b as one of the strongest candidates getting accumulated to the sites of early BCR activation. In this report, we follow up on this finding and investigate the localisation and function of Vti1b in B cells. We found that GFP-fused Vti1b was concentrated at the Golgi complex, around the MTOC, as well as in the Rab7+ lysosomal vesicles in the cell periphery. Upon BCR activation with soluble antigen, Vti1b showed partial localization to the internalized antigen vesicles, especially in the periphery of the cell. Moreover, upon BCR activation using surface-bound antigen, Vti1b polarised to the immunological synapse, colocalising with the Golgi complex, and with lysosomes at actin foci. To test for a functional role of Vti1b in early B cell activation, we used primary B cells isolated from Vit1b-deficient mouse. However, we found no functional defects in BCR signalling, immunological synapse formation, or processing and presentation of the internalized antigen, suggesting that the loss of Vti1b in B cells could be compensated by its close homologue Vti1a or other SNAREs.

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Section: Discussionmentioning

confidence: 99%

The SNARE protein Vti1b is recruited to the sites of BCR activation but is redundant for antigen internalisation, processing and presentation

Music

Tejeda-González

Cunha

et al. 2022

Front. Cell Dev. Biol.

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“…To determine how the proteasome negatively regulates actin accumulation at the IS of B cells, we evaluated whether the levels of actin polymerizing factors, which are targets of proteasome degradation ( Schaefer et al, 2012 ), changed in Ecm29-silenced cells. The levels of actin polymerizing factors, Arp2, WASp, and HS1, which have been shown to play a role in B cells ( Bolger-Munro et al, 2019 ; Roper et al, 2019 ) were quantified in control and Ecm29-silenced B cells, by immunoblot. We found reduced levels of HS1 in Ecm29-silenced cells, whereas Arp2 or WASp remained unchanged ( Figures 4H,I ).…”

Section: Resultsmentioning

confidence: 99%

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

Ibañez-Vega

Valle

Sáez

et al. 2021

Front. Cell Dev. Biol.

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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.

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B cells extract antigens using Arp2/3-generated actin foci interspersed with linear filaments

Cited by 2 publications

References 33 publications

The SNARE protein Vti1b is recruited to the sites of BCR activation but is redundant for antigen internalisation, processing and presentation

The SNARE protein Vti1b is recruited to the sites of BCR activation but is redundant for antigen internalisation, processing and presentation

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

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