A G protein-coupled receptor with a lipid kinase domain is involved in cell-density sensing. Academic Article uri icon


  • 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.

published proceedings

  • Curr Biol

altmetric score

  • 3

author list (cited authors)

  • Bakthavatsalam, D., Brazill, D., Gomer, R. H., Eichinger, L., Rivero, F., & Noegel, A. A.

citation count

  • 19

complete list of authors

  • Bakthavatsalam, Deenadayalan||Brazill, Derrick||Gomer, Richard H||Eichinger, Ludwig||Rivero, Francisco||Noegel, Angelika A

publication date

  • January 2007