Remodeling of secretory lysosomes during education tunes functional potential in NK cells.
Aminopyridines
/ pharmacology
Animals
Granzymes
/ metabolism
Heterocyclic Compounds, 3-Ring
/ pharmacology
Humans
K562 Cells
Killer Cells, Natural
/ drug effects
Lysosomal-Associated Membrane Protein 1
/ genetics
Lysosomes
/ drug effects
Mice
Receptors, KIR
/ metabolism
Signal Transduction
/ drug effects
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
31 01 2019
31 01 2019
Historique:
received:
09
07
2018
accepted:
04
01
2019
entrez:
2
2
2019
pubmed:
2
2
2019
medline:
9
4
2019
Statut:
epublish
Résumé
Inhibitory signaling during natural killer (NK) cell education translates into increased responsiveness to activation; however, the intracellular mechanism for functional tuning by inhibitory receptors remains unclear. Secretory lysosomes are part of the acidic lysosomal compartment that mediates intracellular signalling in several cell types. Here we show that educated NK cells expressing self-MHC specific inhibitory killer cell immunoglobulin-like receptors (KIR) accumulate granzyme B in dense-core secretory lysosomes that converge close to the centrosome. This discrete morphological phenotype is independent of transcriptional programs that regulate effector function, metabolism and lysosomal biogenesis. Meanwhile, interference of signaling from acidic Ca
Identifiants
pubmed: 30705279
doi: 10.1038/s41467-019-08384-x
pii: 10.1038/s41467-019-08384-x
pmc: PMC6355880
doi:
Substances chimiques
6-amino-N-(3-(4-(4-morpholinyl)pyrido(3',2'-4,5)furo(3,2-d)pyrimidin-2-yl)phenyl)-3-pyridinecarboxamide
0
Aminopyridines
0
Heterocyclic Compounds, 3-Ring
0
Lysosomal-Associated Membrane Protein 1
0
Receptors, KIR
0
Granzymes
EC 3.4.21.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
514Commentaires et corrections
Type : CommentIn
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