The cytoplasmic tail of invariant chain regulates endosome fusion and morphology.
The major histocompatibility complex class II associated invariant chain (Ii) has been shown to inhibit endocytic transport and to increase the size of endosomes. We have recently found that this property has a significant impact on antigen processing and presentation. Here, we show in a cell-free endosome fusion assay that expression of Ii can increase fusion after phosphatidylinositol 3-kinase activity is blocked by wortmannin. In live cells wortmannin was also not able to block formation of the Ii-induced enlarged endosomes. The effects of Ii on endosomal transport and morphology depend on elements within the cytoplasmic tail. Data from mutagenesis analysis and nuclear magnetic resonance-based structure calculations of the Ii cytoplasmic tail demonstrate that free negative charges that are not involved in internal salt bridges are essential for both interactions between the tails and for the formation of enlarged endosomes. This correlation indicates that it is interactions between the Ii cytoplasmic tails that are involved in endosome fusion. The combined data from live cells, cell-free assays, and molecular dynamic simulations suggest that Ii molecules on different vesicles can promote endosome docking and fusion and thereby control endosomal traffic of membrane proteins and endosomal content.
Nordeng
Tommy W
TW
Centre d'Immunologie de Marseille-Luminy, Centre National de la Recherche Scientifique-INSERM-Univ-Med, 13288 Marseille, Cedex 09, France.
Gregers
Tone F
TF
Kongsvik
Thomas Lasker
TL
Méresse
Stéphane
S
Gorvel
Jean-Pierre
JP
Jourdan
Fabrice
F
Motta
Andrea
A
Bakke
Oddmund
O
D000595:Amino Acid Sequence; D000818:Animals; D000944:Antigens, Differentiation, B-Lymphocyte / Q000737:chemistry* / Q000502:physiology*; D019556:COS Cells; D002459:Cell Fusion; D002460:Cell Line; D002522:Chlorocebus aethiops; D004285:Dogs; D004705:Endocytosis / Q000502:physiology; D011992:Endosomes / Q000502:physiology* / Q000648:ultrastructure*; D000949:Histocompatibility Antigens Class II / Q000737:chemistry* / Q000502:physiology*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D018715:Microscopy, Video; D018832:Molecular Chaperones / Q000502:physiology; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry; D017433:Protein Structure, Secondary; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D014162:Transfection; D014617:Vacuoles / Q000502:physiology / Q000648:ultrastructure
D000944:Antigens, Differentiation, B-Lymphocyte; D000949:Histocompatibility Antigens Class II; D018832:Molecular Chaperones; D010446:Peptide Fragments; D011994:Recombinant Proteins; C045084:invariant chain