Possible role of deep tubular invaginations of the plasma membrane in MHC-I trafficking.
Tubules and vesicles are membrane carriers involved in traffic along the endocytic and secretory routes. The small GTPase Arf6 regulates a recycling branch of short dynamic tubular intermediates used by major histocompatibility class I (MHC-I) molecules to traffic through vesicles between endosomes and the plasma membrane. We observed that Arf6 also affects a second network of very long and stable tubules containing MHC-I, many of which correspond to deep invaginations of the plasma membrane. Treatment with wortmannin, an inhibitor of phosphatidylinositol-3-phosphate kinase, prevents formation of the short dynamic tubules while increasing the number of the long and very stable ones. Expression of NefAAAA, a mutant form of HIV Nef, increases the number of cells containing the stable tubules, and is used here as a tool to facilitate their study. Photoactivation of NefAAAA-PA-GFP demonstrates that this molecule traffics from endosomes to the tubules. Finally, live-cell imaging also shows internalization of MHC-I molecules into these tubules, suggesting that this is an additional route for MHC-I traffic.
Massol
Ramiro H
RH
Department of Cell Biology and The CBR Institute for Biomedical Research, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA.
Larsen
Jakob E
JE
Kirchhausen
Tomas
T
D000089982:ADP-Ribosylation Factor 6; D020727:ADP-Ribosylation Factors / Q000235:genetics; D000730:Androstadienes / Q000494:pharmacology; D045744:Cell Line, Tumor; D021961:Cell Membrane Structures / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D022162:Cytoplasmic Vesicles / Q000378:metabolism; D004705:Endocytosis / Q000502:physiology; D011992:Endosomes / Q000378:metabolism; D015693:Gene Products, nef / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000032:analysis / Q000378:metabolism*; D006801:Humans; D008854:Microscopy, Electron; D008954:Models, Biological; D009154:Mutation / Q000235:genetics; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D021381:Protein Transport / Q000502:physiology; D014161:Transduction, Genetic; D014162:Transfection; D000077191:Wortmannin
D000089982:ADP-Ribosylation Factor 6; D020727:ADP-Ribosylation Factors; D000730:Androstadienes; D015693:Gene Products, nef; D015395:Histocompatibility Antigens Class I; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors; D000077191:Wortmannin; C000715348:ARF6 protein, human