A G protein-coupled receptor with a lipid kinase domain is involved in cell-density sensing.
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.
Bakthavatsalam
Deenadayalan
D
Center for Biochemistry, Institute for Biochemistry I, Medical Faculty and Center for Molecular Medicine Cologne, University of Cologne, D-50931 Cologne, Germany.
Brazill
Derrick
D
Gomer
Richard H
RH
Eichinger
Ludwig
L
Rivero
Francisco
F
Noegel
Angelika A
AA
D000818:Animals; D015815:Cell Adhesion Molecules / Q000378:metabolism; D004023:Dictyostelium / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D011992:Endosomes / Q000378:metabolism; D044385:GTP-Binding Protein alpha Subunits / Q000378:metabolism; D005786:Gene Expression Regulation; D050356:Lipid Metabolism; D008954:Models, Biological; D010770:Phosphotransferases / Q000737:chemistry*; D017434:Protein Structure, Tertiary; D015800:Protozoan Proteins / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*
D015815:Cell Adhesion Molecules; D044385:GTP-Binding Protein alpha Subunits; D015800:Protozoan Proteins; D043562:Receptors, G-Protein-Coupled; C013065:cell aggregation factors; D010770:Phosphotransferases