Nature Immunology
6, 1020 - 1028 (2005)
Published online: 18 September 2005; | doi:10.1038/ni1250
Involvement of caspase-cleaved and intact adaptor protein 1 complex in endosomal remodeling in maturing dendritic cellsLaura Santambrogio1, 2, Ilaria Potolicchio3, Shawn P Fessler2, Siew-Heng Wong1, Graça Raposo3
& Jack L Strominger1, 41
Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA. 2
Department of Pathology, Albert Einstein College of Medicine, New York, New York 10461, USA. 3
Institut Curie, CNRS, UMR 144, 75005 Paris, France. 4
Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138, USA.
Correspondence should be addressed to Jack L Strominger jlstrom@fas.harvard.edu or Laura Santambrogio lsantamb@aecom.yu.edu 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  1- and  -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.
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