| Structural highlights
Function
CLC9A_HUMAN Functions as an endocytic receptor on a small subset of myeloid cells specialized for the uptake and processing of material from dead cells. Recognizes filamentous form of actin in association with particular actin-binding domains of cytoskeletal proteins, including spectrin, exposed when cell membranes are damaged, and mediate the cross-presentation of dead-cell associated antigens in a Syk-dependent manner.[1] [2]
Publication Abstract from PubMed
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 conserved tryptophans in the ligand recognition site. Mutation of these residues ablated CLEC9A binding to damaged cells and to the isolated ligand complexes. We propose that Clec9A provides targeted recruitment of the adaptive immune system during infection and can also be utilized to enhance immune responses generated by vaccines.
The Dendritic Cell Receptor Clec9A Binds Damaged Cells via Exposed Actin Filaments.,Zhang JG, Czabotar PE, Policheni AN, Caminschi I, San Wan S, Kitsoulis S, Tullett KM, Robin AY, Brammananth R, van Delft MF, Lu J, O'Reilly LA, Josefsson EC, Kile BT, Chin WJ, Mintern JD, Olshina MA, Wong W, Baum J, Wright MD, Huang DC, Mohandas N, Coppel RL, Colman PM, Nicola NA, Shortman K, Lahoud MH Immunity. 2012 Apr 20;36(4):646-57. Epub 2012 Apr 5. PMID:22483802[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Sancho D, Mourao-Sa D, Joffre OP, Schulz O, Rogers NC, Pennington DJ, Carlyle JR, Reis e Sousa C. Tumor therapy in mice via antigen targeting to a novel, DC-restricted C-type lectin. J Clin Invest. 2008 Jun;118(6):2098-110. doi: 10.1172/JCI34584. PMID:18497879 doi:10.1172/JCI34584
- ↑ Zhang JG, Czabotar PE, Policheni AN, Caminschi I, San Wan S, Kitsoulis S, Tullett KM, Robin AY, Brammananth R, van Delft MF, Lu J, O'Reilly LA, Josefsson EC, Kile BT, Chin WJ, Mintern JD, Olshina MA, Wong W, Baum J, Wright MD, Huang DC, Mohandas N, Coppel RL, Colman PM, Nicola NA, Shortman K, Lahoud MH. The Dendritic Cell Receptor Clec9A Binds Damaged Cells via Exposed Actin Filaments. Immunity. 2012 Apr 20;36(4):646-57. Epub 2012 Apr 5. PMID:22483802 doi:10.1016/j.immuni.2012.03.009
- ↑ Zhang JG, Czabotar PE, Policheni AN, Caminschi I, San Wan S, Kitsoulis S, Tullett KM, Robin AY, Brammananth R, van Delft MF, Lu J, O'Reilly LA, Josefsson EC, Kile BT, Chin WJ, Mintern JD, Olshina MA, Wong W, Baum J, Wright MD, Huang DC, Mohandas N, Coppel RL, Colman PM, Nicola NA, Shortman K, Lahoud MH. The Dendritic Cell Receptor Clec9A Binds Damaged Cells via Exposed Actin Filaments. Immunity. 2012 Apr 20;36(4):646-57. Epub 2012 Apr 5. PMID:22483802 doi:10.1016/j.immuni.2012.03.009
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