Uncommon endocytic and trafficking pathway of the natural killer cell CD94/NKG2A inhibitory receptor.
The CD94/NKG2A inhibitory receptor, expressed by natural killer and T cells, is constantly exposed to its HLA-E ligand expressed by surrounding cells. Ligand exposure often induces receptor downregulation. For CD94/NKG2A, this could potentiate activation receptor(s) induced responses to normal bystander cells. We investigated CD94/NKG2A endocytosis and found that it occurs by an amiloride-sensitive, Rac1-dependent macropinocytic-like process; however, it does not require clathrin, dynamin, ADP ribosylation factor-6, phosphoinositide-3 kinase or the actin cytoskeleton. Once endocytosed, CD94/NKG2A traffics to early endosomal antigen 1(+), Rab5(+) early endosomes. It does appear in Rab4(+) early/sorting endosome, but, in the time period examined, fails to reach Rab11(+) recycling or Rab7(+) late endosomes or lysosome-associated membrane protein-1(+) lysosomes. These results indicate that CD94/NKG2A utilizes a previously undescribed endocytic mechanism coupled with an abbreviated trafficking pattern, perhaps to insure surface expression.
Masilamani
Madhan
M
Receptor Cell Biology Section, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA.
Narayanan
Sriram
S
Prieto
Martha
M
Borrego
Francisco
F
Coligan
John E
JE
D000089982:ADP-Ribosylation Factor 6; D034281:Dynamins / Q000037:antagonists & inhibitors; D004705:Endocytosis; D019084:Fluorescent Antibody Technique, Indirect; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D006835:Hydrazones / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D055654:NK Cell Lectin-Like Receptor Subfamily C; D051920:NK Cell Lectin-Like Receptor Subfamily D / Q000276:immunology / Q000378:metabolism*; D021381:Protein Transport; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D011971:Receptors, Immunologic / Q000276:immunology / Q000378:metabolism*; D055607:Receptors, Natural Killer Cell
D000089982:ADP-Ribosylation Factor 6; D006835:Hydrazones; C527054:KLRC1 protein, human; C511794:N'-(3,4-dihydroxybenzylidene)-3-hydroxy-2-naphthahydrazide; D055654:NK Cell Lectin-Like Receptor Subfamily C; D051920:NK Cell Lectin-Like Receptor Subfamily D; D034741:RNA, Small Interfering; D011971:Receptors, Immunologic; D055607:Receptors, Natural Killer Cell; D049452:Green Fluorescent Proteins; C000715348:ARF6 protein, human; D034281:Dynamins