RRC ID 59991
Author Kinoshita D, Sakurai C, Morita M, Tsunematsu M, Hori N, Hatsuzawa K.
Title Syntaxin 11 regulates the stimulus-dependent transport of Toll-like receptor 4 to the plasma membrane by cooperating with SNAP-23 in macrophages.
Journal 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.
Volume 30(9)
Pages 1085-1097
Published 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
Times Cited 1
Human and Animal Cells J774