Document Detail

Uncommon endocytic and trafficking pathway of the natural killer cell CD94/NKG2A inhibitory receptor.
MedLine Citation:
PMID:  18363778     Owner:  NLM     Status:  MEDLINE    
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.
Madhan Masilamani; Sriram Narayanan; Martha Prieto; Francisco Borrego; John E Coligan
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Intramural     Date:  2008-03-19
Journal Detail:
Title:  Traffic (Copenhagen, Denmark)     Volume:  9     ISSN:  1600-0854     ISO Abbreviation:  Traffic     Publication Date:  2008 Jun 
Date Detail:
Created Date:  2008-05-09     Completed Date:  2008-07-16     Revised Date:  2009-06-22    
Medline Journal Info:
Nlm Unique ID:  100939340     Medline TA:  Traffic     Country:  Denmark    
Other Details:
Languages:  eng     Pagination:  1019-34     Citation Subset:  IM    
Receptor Cell Biology Section, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA.
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MeSH Terms
Dynamins / antagonists & inhibitors
Fluorescent Antibody Technique, Indirect
Green Fluorescent Proteins / metabolism
Hydrazones / pharmacology
Killer Cells, Natural / immunology*,  metabolism
NK Cell Lectin-Like Receptor Subfamily C
NK Cell Lectin-Like Receptor Subfamily D / immunology,  metabolism*
Protein Transport
RNA Interference
RNA, Small Interfering / metabolism
Receptors, Immunologic / immunology,  metabolism*
Receptors, Natural Killer Cell
Reg. No./Substance:
0/Hydrazones; 0/KLRC1 protein, human; 0/N'-(3,4-dihydroxybenzylidene)-3-hydroxy-2-naphthahydrazide; 0/NK Cell Lectin-Like Receptor Subfamily C; 0/NK Cell Lectin-Like Receptor Subfamily D; 0/RNA, Small Interfering; 0/Receptors, Immunologic; 0/Receptors, Natural Killer Cell; 147336-22-9/Green Fluorescent Proteins; EC

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