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Uncommon Endocytic and Trafficking Pathway of the Natural Killer Cell CD94/NKG2A Inhibitory Receptor
Author(s) -
Masilamani Madhan,
Narayanan Sriram,
Prieto Martha,
Borrego Francisco,
Coligan John E.
Publication year - 2008
Publication title -
traffic
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.677
H-Index - 130
eISSN - 1600-0854
pISSN - 1398-9219
DOI - 10.1111/j.1600-0854.2008.00738.x
Subject(s) - endosome , endocytic cycle , microbiology and biotechnology , endocytosis , biology , dynamin , internalization , clathrin , lysosome , downregulation and upregulation , receptor , biochemistry , intracellular , gene , enzyme
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.