A G protein-coupled receptor with a lipid kinase domain is involved in cell-density sensing

Curr Biol. 2007 May 15;17(10):892-7. doi: 10.1016/j.cub.2007.04.029. Epub 2007 May 3.

Abstract

One mechanism multicellular structures use for controlling cell number [1, 2] involves the secretion and sensing of a factor, such as leptin [3] or myostatin [4], in mammals. Dictyostelium cells secrete autocrine factors for sensing cell density prior to aggregation and multicellular development [5, 6] such as CMF (conditioned-medium factor), which enables starving cells to respond to cAMP pulses [7-9]. Its actions are mediated by two receptors. CMFR1 activates a G protein-independent signaling pathway regulating gene expression [10]. An unknown Galpha1-dependent receptor activates phospholipase C (PLC), which regulates the lifetime of Galpha2-GTP [11-13]. Here, we describe RpkA, an unusual seven-transmembrane receptor that is fused to a C-terminal PIP5 kinase domain and that localizes in membranes of a late endosomal compartment. Loss of RpkA resulted in formation of persistent loose aggregates and altered expression of cAMP-regulated genes. The developmental defect can be rescued by full-length RpkA and the transmembrane domain only. The PIP5 kinase domain is dispensable for the developmental role of RpkA. rpkA- cells secrete and bind CMF but are unable to induce downstream responses. Inactivation of Galpha1, a negative regulator of CMF signaling, rescued the developmental defect of the rpkA- cells, suggesting that RpkA actions are mediated by Galpha1.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Cell Adhesion Molecules / metabolism
  • Dictyostelium / genetics
  • Dictyostelium / growth & development
  • Dictyostelium / metabolism*
  • Endosomes / metabolism
  • GTP-Binding Protein alpha Subunits / metabolism
  • Gene Expression Regulation
  • Lipid Metabolism
  • Models, Biological
  • Phosphotransferases / chemistry*
  • Protein Structure, Tertiary
  • Protozoan Proteins / chemistry
  • Protozoan Proteins / metabolism
  • Protozoan Proteins / physiology*
  • Receptors, G-Protein-Coupled / chemistry
  • Receptors, G-Protein-Coupled / metabolism
  • Receptors, G-Protein-Coupled / physiology*
  • Signal Transduction / physiology*

Substances

  • Cell Adhesion Molecules
  • GTP-Binding Protein alpha Subunits
  • Protozoan Proteins
  • Receptors, G-Protein-Coupled
  • cell aggregation factors
  • Phosphotransferases