Proteomic-based identification of CD4-interacting proteins in human primary macrophages |
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Authors: | Raposo Rui André Saraiva Thomas Benjamin Ridlova Gabriela James William |
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Institution: | Sir William Dunn School of Pathology, University of Oxford, Oxford, United Kingdom. andre.saraivaraposo@path.ox.ac.uk |
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Abstract: | BackgroundHuman macrophages (Mφ) express low levels of CD4 glycoprotein, which is
constitutively recycled, and 40–50% of its localization is
intracellular at steady-state. Although CD4-interacting proteins in lymphoid
cells are well characterised, little is known about the CD4 protein
interaction-network in human Mφ, which notably lack LCK, a Src family
protein tyrosine kinase believed to stabilise CD4 at the surface of T cells.
As CD4 is the main cellular receptor used by HIV-1, knowledge of its
molecular interactions is important for the understanding of viral infection
strategies.Methodology/Principal FindingsWe performed large-scale anti-CD4 immunoprecipitations in human primary
Mφ followed by high-resolution mass spectrometry analysis to elucidate
the protein interaction-network involved in induced CD4 internalization and
degradation. Proteomic analysis of CD4 co-immunoisolates in resting Mφ
showed CD4 association with a range of proteins found in the cellular
cortex, membrane rafts and components of clathrin-adaptor proteins, whereas
in induced internalization and degradation CD4 is associated with components
of specific signal transduction, transport and the proteasome.Conclusions/SignificanceThis is the first time that the anti-CD4 co-immunoprecipitation sub-proteome
has been analysed in human primary Mφ. Our data have identified
important Mφ cell surface CD4-interacting proteins, as well as
regulatory proteins involved in internalization and degradation. The data
give valuable insights into the molecular pathways involved in the
regulation of CD4 expression in Mφ and provide candidates/targets for
further biochemical studies. |
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