Rhodopsin-family receptors associate with small G proteins to activate phospholipase D

R Mitchell, D McCulloch, E Lutz, M Johnson, C MacKenzie, M Fennell, G Fink, W Zhou, S C Sealfon

Research output: Contribution to journalArticlepeer-review

Abstract

G-protein-coupled receptors of the rhodopsin family transduce many important neural and endocrine signals. These receptors activate heterotrimeric G proteins and in many cases also cause activation of phospholipase D, an enzyme that can be controlled by the small G proteins ARF and RhoA. Here we show that the activation of phospholipase D that is induced by many, but not all, Ca2+-mobilizing G-protein-coupled receptors is sensitive to inhibitors of ARF and of RhoA. Receptors of this type were co-immunoprecipitated with ARF or RhoA on exposure to agonists, and the effects of GTP analogues on ligand binding to the receptor changed to a profile that is characteristic of small G proteins. These receptors contain the amino-acid sequence AsnProXXTyr in their seventh transmembrane domain, whereas receptors capable of activating phospholipase D without involving ARF contain the sequence AspProXXTyr. Mutation of this latter sequence to AsnProXXTyr in the gonadotropin-releasing hormone receptor conferred sensitivity to an inhibitor of ARF, and the reciprocal mutation in the 5-HT2A receptor for 5-hydroxy-tryptamine reduced its sensitivity to the inhibitor. Receptors carrying the AsnProXXTyr motif thus seem to form functional complexes with ARF and RhoA.
Original languageEnglish
Pages (from-to)411-4
Number of pages4
JournalNature
Volume392
Issue number6674
DOIs
Publication statusPublished - 26 Mar 1998

Keywords

  • ADP-Ribosylation Factors
  • Animals
  • Brefeldin A
  • COS Cells
  • Cyclopentanes
  • Enzyme Activation
  • Estrenes
  • GTP-Binding Proteins
  • Guanosine Triphosphate
  • Humans
  • Male
  • Phospholipase D
  • Pyrrolidinones
  • Rats
  • Receptor, Muscarinic M3
  • Receptors, LHRH
  • Receptors, Muscarinic
  • Recombinant Proteins
  • Rhodopsin
  • Tumor Cells, Cultured
  • Type C Phospholipases
  • rhoA GTP-Binding Protein

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