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    Ligand binding determines whether CD46 is internalized by clathrin-coated pits or macropinocytosis

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    Author
    Crimeen-Irwin, B; Ellis, S; Christiansen, D; Ludford-Menting, MJ; Milland, J; Lanteri, M; Loveland, BE; Gerlier, D; Russell, SM
    Date
    2003-11-21
    Source Title
    Journal of Biological Chemistry
    Publisher
    AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
    University of Melbourne Author/s
    Christiansen, Dale; Russell, Sarah; MILLAND, JULIE; Ludford-Menting, Mandy
    Affiliation
    Pathology
    Metadata
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    Document Type
    Journal Article
    Citations
    Crimeen-Irwin, B., Ellis, S., Christiansen, D., Ludford-Menting, M. J., Milland, J., Lanteri, M., Loveland, B. E., Gerlier, D. & Russell, S. M. (2003). Ligand binding determines whether CD46 is internalized by clathrin-coated pits or macropinocytosis. JOURNAL OF BIOLOGICAL CHEMISTRY, 278 (47), pp.46927-46937. https://doi.org/10.1074/jbc.M308261200.
    Access Status
    This item is currently not available from this repository
    URI
    http://hdl.handle.net/11343/26265
    DOI
    10.1074/jbc.M308261200
    Description

    C1 - Journal Articles Refereed

    Abstract
    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.
    Keywords
    Immunology not elsewhere classified; Infectious Diseases; Infectious Diseases

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