| RRC ID |
59991
|
| 著者 |
Kinoshita D, Sakurai C, Morita M, Tsunematsu M, Hori N, Hatsuzawa K.
|
| タイトル |
Syntaxin 11 regulates the stimulus-dependent transport of Toll-like receptor 4 to the plasma membrane by cooperating with SNAP-23 in macrophages.
|
| ジャーナル |
Mol Biol Cell
|
| Abstract |
Syntaxin 11 (stx11) is a soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) that is selectively expressed in immune cells; however, its precise role in macrophages is unclear. We showed that stx11 knockdown reduces the phagocytosis of Escherichia coli in interferon-γ-activated macrophages. stx11 knockdown decreased Toll-like receptor 4 (TLR4) localization on the plasma membrane without affecting total expression. Plasma membrane-localized TLR4 was primarily endocytosed within 1 h by lipopolysaccharide (LPS) stimulation and gradually relocalized 4 h after removal of LPS. This relocalization was significantly impaired by stx11 knockdown. The lack of TLR4 transport to the plasma membrane is presumably related to TLR4 degradation in acidic endosomal organelles. Additionally, an immunoprecipitation experiment suggested that stx11 interacts with SNAP-23, a plasma membrane-localized SNARE protein, whose depletion also inhibits TLR4 replenishment in LPS-stimulated cells. Using an intramolecular Förster resonance energy transfer (FRET) probe for SNAP-23, we showed that the high FRET efficiency caused by LPS stimulation is reduced by stx11 knockdown. These findings suggest that stx11 regulates the stimulus-dependent transport of TLR4 to the plasma membrane by cooperating with SNAP-23 in macrophages. Our results clarify the regulatory mechanisms underlying intracellular transport of TLR4 and have implications for microbial pathogenesis and immune responses.
|
| 巻・号 |
30(9)
|
| ページ |
1085-1097
|
| 公開日 |
2019-4-15
|
| DOI |
10.1091/mbc.E18-10-0653
|
| PMID |
30811271
|
| PMC |
PMC6724512
|
| MeSH |
Animals
Cell Line
Cell Membrane / metabolism
Endocytosis / physiology
Endosomes / metabolism
Gene Knockdown Techniques
Macrophages / metabolism
Membrane Fusion
Mice
Mice, Inbred BALB C
Phagocytosis / physiology
Protein Binding
Protein Transport
Qa-SNARE Proteins / genetics
Qa-SNARE Proteins / metabolism*
Qb-SNARE Proteins / metabolism*
Qc-SNARE Proteins / metabolism*
Toll-Like Receptor 4 / genetics
Toll-Like Receptor 4 / metabolism*
|
| IF |
3.905
|
| 引用数 |
1
|
| リソース情報 |
| ヒト・動物細胞 |
J774 |
