Regulating G protein-coupled receptors by topological inversion

Bray Denard, Sungwon Han, Jung Yeon Kim, Elliott M. Ross, Jin Ye

Research output: Contribution to journalArticle

Abstract

G protein-coupled receptors (GPCRs) are a family of proteins containing seven transmembrane helices, with the N- and C-terminus of the protein located at the extracellular space and cytosol, respectively. Here, we report that ceramide or related sphingolipids might invert the topology of many GPCRs that contain a GXXXN motif in their first transmembrane helix. The functional significance of this topological regulation is illustrated by the CCR5 chemokine receptor. In the absence of lipopolysaccharide (LPS), CCR5 adopts a topology consistent with that of GPCR, allowing mouse peritoneal macrophages to migrate toward its ligand CCL5. LPS stimulation results in increased production of dihydroceramide, which inverts the topology of CCR5, preventing macrophages from migrating toward CCL5. These results suggest that GPCRs may not always adopt the same topology and can be regulated through topological inversion. Editorial note: This article has been through an editorial process in which the authors decide how to respond to the issues raised during peer review. The Reviewing Editor's assessment is that major issues remain unresolved (see decision letter).

Original languageEnglish (US)
JournaleLife
Volume8
DOIs
StatePublished - Mar 5 2019

Fingerprint

G-Protein-Coupled Receptors
Topology
Macrophages
Lipopolysaccharides
CCR5 Receptors
Sphingolipids
Peer Review
Chemokine Receptors
Ceramides
Extracellular Space
Peritoneal Macrophages
Protein C
Cytosol
Proteins
Ligands

Keywords

  • biochemistry
  • cell biology
  • ceramide
  • chemical biology
  • chemotaxis
  • G protein-coupled receptor
  • mouse
  • topology

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

Cite this

Regulating G protein-coupled receptors by topological inversion. / Denard, Bray; Han, Sungwon; Kim, Jung Yeon; Ross, Elliott M.; Ye, Jin.

In: eLife, Vol. 8, 05.03.2019.

Research output: Contribution to journalArticle

Denard, Bray ; Han, Sungwon ; Kim, Jung Yeon ; Ross, Elliott M. ; Ye, Jin. / Regulating G protein-coupled receptors by topological inversion. In: eLife. 2019 ; Vol. 8.
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