Journal article
The Dendritic Cell Receptor Clec9A Binds Damaged Cells via Exposed Actin Filaments
JG Zhang, PE Czabotar, AN Policheni, I Caminschi, S San Wan, S Kitsoulis, KM Tullett, AY Robin, R Brammananth, MF van Delft, J Lu, LA O'Reilly, EC Josefsson, BT Kile, WJ Chin, JD Mintern, MA Olshina, W Wong, J Baum, MD Wright Show all
Immunity | CELL PRESS | Published : 2012
Abstract
The immune system must distinguish viable cells from cells damaged by physical and infective processes. The damaged cell-recognition molecule Clec9A is expressed on the surface of the mouse and human dendritic cell subsets specialized for the uptake and processing of material from dead cells. Clec9A recognizes a conserved component within nucleated and nonnucleated cells, exposed when cell membranes are damaged. We have identified this Clec9A ligand as a filamentous form of actin in association with particular actin-binding domains of cytoskeletal proteins. We have determined the crystal structure of the human CLEC9A C-type lectin domain and propose a functional dimeric structure with conser..
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Awarded by Human Frontier Science Program
Funding Acknowledgements
We thank A. Cowman and R. Simpson for critical discussions and L. Zhang for his assistance with CD measurements. We thank L. Connolly, H. Patsiouras, and T. Nebl for MS sequencing analysis. Crystallization trials were performed at the Bio21 Collaborative Crystallisation Centre, Australia. Diffraction data were collected at the Australian Synchrotron and we thank staff for their assistance. This work was supported by the National Health and Medical Research Council of Australia (NHMRC) program grants 454465 (KS.), 461219 (N.A.N., J.-G.Z.), and 461221 (D.C.S.H.), project grants 575546 (KS., M.H.L., IC.) and 1009145 (L.O.R.), Human Frontier Science Program (J.B.), Australian Research Council Future Fellowships (P.E.C., J.B.), NHMRC fellowships (KS., P.M.C., N.A.N., D.C.S.H.), NHMRC Career Development Fellowship (J.D.M.), Australian Cancer Research Foundation (P.M.C., D.C.S.H.), Leukemia & Lymphoma Society Grant SCOR 7413 (D.C.S.H., L.O.R.) and Fellowship (E.C.J.), Melbourne University International Research Scholarship (M.F.v.D.), and Cancer Council Victoria Postdoctoral Research Fellowship (M.F.v.D.). This work was made possible through Victorian State Government Operational Infrastructure Support and Australian Government NHMRC IRIIS.