title: Involvement of caspase-cleaved and intact adaptor protein 1 complex in endosomal remodeling in maturing dendritic cells.
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 beta1- and gamma-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.
authors.affiliation: Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA. lsantamb@aecom.yu.edu
authors.forename: Laura
authors.initials: L
authors.lastname: Santambrogio
authors.forename: Ilaria
authors.initials: I
authors.lastname: Potolicchio
authors.forename: Shawn P
authors.initials: SP
authors.lastname: Fessler
authors.forename: Siew-Heng
authors.initials: SH
authors.lastname: Wong
authors.forename: Graça
authors.initials: G
authors.lastname: Raposo
authors.forename: Jack L
authors.initials: JL
authors.lastname: Strominger
mesh_terms: D033961:Adaptor Protein Complex 1 / Q000378:metabolism*; D033966:Adaptor Protein Complex beta Subunits / Q000378:metabolism; D000818:Animals; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism*; D002454:Cell Differentiation; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D017434:Protein Structure, Tertiary; D021381:Protein Transport
chemical_list: D033961:Adaptor Protein Complex 1; D033966:Adaptor Protein Complex beta Subunits; C510064:Ap1b1 protein, mouse; D000949:Histocompatibility Antigens Class II; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases