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Home List of Titles Ligand binding determines whether CD46 is internalized by clathrin-coated pits or macropinocytosis
Please use this identifier to cite or link to this item: http://hdl.handle.net/1959.3/81190
- Ligand binding determines whether CD46 is internalized by clathrin-coated pits or macropinocytosis
- Crimeen-Irwin, Blessing; Ellis, Sarah; Christiansen, Dale; Ludford-Menting, Mandy J.; Milland, Julie; Lanteri, Marc; Loveland, Bruce E.; Gerlier, Denis; Russell, Sarah M.
- CD46 is a ubiquitous human cell surface receptor for the complement components C3b and C4b and for various pathogens, including the measles virus and human herpes virus 6. Ligand binding to CD46 affects (i) protection of autologous cells from complement attack by breakdown of complement components, (ii) intracellular signals that affect the regulation of immune cell function, (iii) antigen presentation, and (iv) down-regulation of cell surface CD46. Recent evidence indicates that CD46 signaling can link innate and acquired immune function. The molecular mechanisms for these processes and the importance of intracellular trafficking of the receptor have not yet been elucidated. We demonstrate here that, in nonlymphoid cells, CD46 is constitutively internalized via clathrin-coated pits, traffics to multivesicular bodies, and is recycled to the cell surface. However, cross-linking of CD46 at the cell surface, by either multivalent antibody or by measles virus, induces pseudopodia that engulf the ligand in a process similar to macropinocytosis, and leads to the degradation of cell surface CD46. Thus, we have elucidated two pathways for CD46 internalization, which are regulated by the valence of cross-linking of CD46 and which utilize either clathrin-coated pits or pseudopodial extension. This has important implications for CD46 signaling, antigen presentation, CD46 down-regulation, and engulfment of pathogens.
- Publication type
- Journal article
- Journal of Biological Chemistry, Vol. 278, no. 47 (Nov 2003), pp. 46927-46937
- Publication year
- FOR Code(s)
- 0601 Biochemistry and Cell Biology; 0904 Chemical Engineering
- CD46; Cells; Clathrin-coated Pits; Immune system; Ligand binding; Macropinocytosis
- American Society for Biochemistry and Molecular Biology
- Publisher URL
- Copyright © 2003 by The American Society for Biochemistry and Molecular Biology, Inc.
- Additional information
- Supported by an Australian Postgraduate Research Award, a National Health and Medical Research Council Howard Florey Centenary Research Fellowship and a Wellcome Senior Research Fellowship in Medical Research.
- Peer reviewed