Home > Publications database > Sphinganine recruits TLR4 adaptors in macrophages and promotes inflammation in murine models of sepsis and melanoma. > print

001     291762
005     20250328112420.0
024 7 _ |a 10.1038/s41467-024-50341-w
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041 _ _ |a English
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100 1 _ |a Hering, Marvin
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245 _ _ |a Sphinganine recruits TLR4 adaptors in macrophages and promotes inflammation in murine models of sepsis and melanoma.
260 _ _ |a [London]
|c 2024
|b Nature Publishing Group UK
336 7 _ |a article
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336 7 _ |a ARTICLE
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520 _ _ |a After recognizing its ligand lipopolysaccharide, Toll-like receptor 4 (TLR4) recruits adaptor proteins to the cell membrane, thereby initiating downstream signaling and triggering inflammation. Whether this recruitment of adaptor proteins is dependent solely on protein-protein interactions is unknown. Here, we report that the sphingolipid sphinganine physically interacts with the adaptor proteins MyD88 and TIRAP and promotes MyD88 recruitment in macrophages. Myeloid cell-specific deficiency in serine palmitoyltransferase long chain base subunit 2, which encodes the key enzyme catalyzing sphingolipid biosynthesis, decreases the membrane recruitment of MyD88 and inhibits inflammatory responses in in vitro bone marrow-derived macrophage and in vivo sepsis models. In a melanoma mouse model, serine palmitoyltransferase long chain base subunit 2 deficiency decreases anti-tumor myeloid cell responses and increases tumor growth. Therefore, sphinganine biosynthesis is required for the initiation of TLR4 signal transduction and serves as a checkpoint for macrophage pattern recognition in sepsis and melanoma mouse models.
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650 _ 7 |a Toll-Like Receptor 4
|2 NLM Chemicals
650 _ 7 |a Myeloid Differentiation Factor 88
|2 NLM Chemicals
650 _ 7 |a Sphingosine
|0 NGZ37HRE42
|2 NLM Chemicals
650 _ 7 |a Tlr4 protein, mouse
|2 NLM Chemicals
650 _ 7 |a Serine C-Palmitoyltransferase
|0 EC 2.3.1.50
|2 NLM Chemicals
650 _ 7 |a safingol
|0 OWA98U788S
|2 NLM Chemicals
650 _ 7 |a Receptors, Interleukin-1
|2 NLM Chemicals
650 _ 7 |a Membrane Glycoproteins
|2 NLM Chemicals
650 _ 7 |a Myd88 protein, mouse
|2 NLM Chemicals
650 _ 7 |a TIRAP protein, mouse
|2 NLM Chemicals
650 _ 7 |a TIRAP protein, human
|2 NLM Chemicals
650 _ 7 |a Lipopolysaccharides
|2 NLM Chemicals
650 _ 2 |a Animals
|2 MeSH
650 _ 2 |a Toll-Like Receptor 4: metabolism
|2 MeSH
650 _ 2 |a Sepsis: metabolism
|2 MeSH
650 _ 2 |a Macrophages: metabolism
|2 MeSH
650 _ 2 |a Myeloid Differentiation Factor 88: metabolism
|2 MeSH
650 _ 2 |a Mice
|2 MeSH
650 _ 2 |a Sphingosine: analogs & derivatives
|2 MeSH
650 _ 2 |a Sphingosine: metabolism
|2 MeSH
650 _ 2 |a Melanoma: metabolism
|2 MeSH
650 _ 2 |a Melanoma: pathology
|2 MeSH
650 _ 2 |a Melanoma: genetics
|2 MeSH
650 _ 2 |a Serine C-Palmitoyltransferase: metabolism
|2 MeSH
650 _ 2 |a Serine C-Palmitoyltransferase: genetics
|2 MeSH
650 _ 2 |a Humans
|2 MeSH
650 _ 2 |a Signal Transduction
|2 MeSH
650 _ 2 |a Disease Models, Animal
|2 MeSH
650 _ 2 |a Inflammation: metabolism
|2 MeSH
650 _ 2 |a Receptors, Interleukin-1: metabolism
|2 MeSH
650 _ 2 |a Receptors, Interleukin-1: genetics
|2 MeSH
650 _ 2 |a Membrane Glycoproteins: metabolism
|2 MeSH
650 _ 2 |a Membrane Glycoproteins: genetics
|2 MeSH
650 _ 2 |a Mice, Inbred C57BL
|2 MeSH
650 _ 2 |a Mice, Knockout
|2 MeSH
650 _ 2 |a HEK293 Cells
|2 MeSH
650 _ 2 |a Lipopolysaccharides
|2 MeSH
700 1 _ |a Madi, Alaa Abdelghani Mohamed
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700 1 _ |a Sandhoff, Roger
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700 1 _ |a Ma, Sicong
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700 1 _ |a Wu, Jingxia
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700 1 _ |a Mieg, Alessa
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700 1 _ |a Richter, Karsten
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700 1 _ |a Bestvater, Felix
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700 1 _ |a Frank, Larissa Johanna
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700 1 _ |a Utikal, Jochen
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700 1 _ |a Umansky, Viktor
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700 1 _ |a Cui, Guoliang
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773 _ _ |a 10.1038/s41467-024-50341-w
|g Vol. 15, no. 1, p. 6067
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|t Nature Communications
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|x 2041-1723
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