Involvement of caspase-cleaved and intact adaptor protein 1 complex in endosomal remodeling in maturing dendritic cells

Laura Santambrogio, Ilaria Potolicchio, Shawn P. Fessler, Siew Heng Wong, Graça Raposo, Jack L. Strominger

Research output: Contribution to journalArticle

63 Scopus citations

Abstract

The involvement of the tetrameric adaptor protein 1 (AP-1) complex in protein sorting in intracellular compartments is not yet completely defined. Here we report that in immature dendritic cells, the β1- and γ-subunits of AP-1 underwent caspase 3-catalyzed cleavage in their hinge regions, resulting in removal of the C-terminal 'ear' domains. Cleavage was inhibited by lipopolysaccharide or caspase inhibitors, each of which led to maturation of the dendritic cells, demonstrated by endosomal remodeling and an increase in surface expression of peptide-loaded major histocompatibility complex class II. Overexpression of similarly truncated AP-1 together with 'silencing' of the endogenous genes in immature dendritic cells did not compromise delivery of major histocompatibility complex class II invariant chain to endosomal compartments. However, after lipopolysaccharide-induced maturation, overexpression of truncated AP-1 and 'silencing' of endogenous genes did result in the anomalous surface accumulation of invariant chain and the peptide-editing molecule H2-DM. Thus, at least one function for intact AP-1 is to retain some proteins in endosomes during the dendritic cell maturation process in which others are allowed to egress to the cell surface.

Original languageEnglish (US)
Pages (from-to)1020-1028
Number of pages9
JournalNature Immunology
Volume6
Issue number10
DOIs
StatePublished - Oct 1 2005

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Santambrogio, L., Potolicchio, I., Fessler, S. P., Wong, S. H., Raposo, G., & Strominger, J. L. (2005). Involvement of caspase-cleaved and intact adaptor protein 1 complex in endosomal remodeling in maturing dendritic cells. Nature Immunology, 6(10), 1020-1028. https://doi.org/10.1038/ni1250