Journal article

RNF41 regulates the damage recognition receptor Clec9A and antigen cross-presentation in mouse dendritic cells

Kirsteen M Tullett, Peck Szee Tan, Hae-Young Park, Ralf B Schittenhelm, Nicole Michael, Rong Li, Antonia N Policheni, Emily Gruber, Cheng Huang, Alex J Fulcher, Jillian C Danne, Peter E Czabotar, Linda M Wakim, Justine D Mintern, Georg Ramm, Kristen J Radford, Irina Caminschi, Meredith O'Keeffe, Jose A Villadangos, Mark D Wright Show all

ELIFE | ELIFE SCIENCES PUBLICATIONS LTD | Published : 2020

Abstract

The dendritic cell receptor Clec9A facilitates processing of dead cell-derived antigens for cross-presentation and the induction of effective CD8+ T cell immune responses. Here, we show that this process is regulated by E3 ubiquitin ligase RNF41 and define a new ubiquitin-mediated mechanism for regulation of Clec9A, reflecting the unique properties of Clec9A as a receptor specialized for delivery of antigens for cross-presentation. We reveal RNF41 is a negative regulator of Clec9A and the cross-presentation of dead cell-derived antigens by mouse dendritic cells. Intriguingly, RNF41 regulates the downstream fate of Clec9A by directly binding and ubiquitinating the extracellular domains of Cle..

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Grants

Funding Acknowledgements

National Health and Medical Research Council Peter E Czabotar Linda M Wakim Justine D Mintern Kristen Radford Irina Caminschi Meredith O'Keeffe Jose Villadangos Mark Wright Marnie E Blewitt William Heath Ken Shortman Anthony W Purcell Nicos A Nicola Jian-Guo Zhang Mireille H Lahoud Cancer Council Victoria Kirsteen M Tullett The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.