% IMPORTANT: The following is UTF-8 encoded. This means that in the presence
% of non-ASCII characters, it will not work with BibTeX 0.99 or older.
% Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or
% “biber”.
@ARTICLE{Hering:291762,
author = {M. Hering$^*$ and A. A. M. Madi$^*$ and R. Sandhoff$^*$ and
S. Ma$^*$ and J. Wu$^*$ and A. Mieg$^*$ and K. Richter$^*$
and K. Mohr$^*$ and N. Knabe$^*$ and D. Stichling$^*$ and G.
Poschet and F. Bestvater$^*$ and L. J. Frank$^*$ and J.
Utikal$^*$ and V. Umansky$^*$ and G. Cui$^*$},
title = {{S}phinganine recruits {TLR}4 adaptors in macrophages and
promotes inflammation in murine models of sepsis and
melanoma.},
journal = {Nature Communications},
volume = {15},
number = {1},
issn = {2041-1723},
address = {[London]},
publisher = {Nature Publishing Group UK},
reportid = {DKFZ-2024-01498},
pages = {6067},
year = {2024},
note = {#EA:D192#EA:A370#LA:D192# / HI-TRON},
abstract = {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.},
keywords = {Animals / Toll-Like Receptor 4: metabolism / Sepsis:
metabolism / Macrophages: metabolism / Myeloid
Differentiation Factor 88: metabolism / Mice / Sphingosine:
analogs $\&$ derivatives / Sphingosine: metabolism /
Melanoma: metabolism / Melanoma: pathology / Melanoma:
genetics / Serine C-Palmitoyltransferase: metabolism /
Serine C-Palmitoyltransferase: genetics / Humans / Signal
Transduction / Disease Models, Animal / Inflammation:
metabolism / Receptors, Interleukin-1: metabolism /
Receptors, Interleukin-1: genetics / Membrane Glycoproteins:
metabolism / Membrane Glycoproteins: genetics / Mice, Inbred
C57BL / Mice, Knockout / HEK293 Cells / Lipopolysaccharides
/ Toll-Like Receptor 4 (NLM Chemicals) / Myeloid
Differentiation Factor 88 (NLM Chemicals) / Sphingosine (NLM
Chemicals) / Tlr4 protein, mouse (NLM Chemicals) / Serine
C-Palmitoyltransferase (NLM Chemicals) / safingol (NLM
Chemicals) / Receptors, Interleukin-1 (NLM Chemicals) /
Membrane Glycoproteins (NLM Chemicals) / Myd88 protein,
mouse (NLM Chemicals) / TIRAP protein, mouse (NLM Chemicals)
/ TIRAP protein, human (NLM Chemicals) / Lipopolysaccharides
(NLM Chemicals)},
cin = {D192 / A370 / A411 / W230 / W210 / D110},
ddc = {500},
cid = {I:(DE-He78)D192-20160331 / I:(DE-He78)A370-20160331 /
I:(DE-He78)A411-20160331 / I:(DE-He78)W230-20160331 /
I:(DE-He78)W210-20160331 / I:(DE-He78)D110-20160331},
pnm = {314 - Immunologie und Krebs (POF4-314)},
pid = {G:(DE-HGF)POF4-314},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:39025856},
pmc = {pmc:PMC11258287},
doi = {10.1038/s41467-024-50341-w},
url = {https://inrepo02.dkfz.de/record/291762},
}