The G alpha subunit G alpha 4 couples to pterin receptors and identifies a signaling pathway that is essential for multicellular development in Dictyostelium.
In this paper, we show that the G alpha subunit G alpha 4 couples to pterin receptors and identifies a signalling pathway that is essential for multicellular development in Dictyostelium. G alpha 4 is developmentally regulated, is essential for proper morphogenesis and spore production, and functions cell nonautonomously. We show that G alpha 4 is coupled to receptors (alpha FAR) that activate chemotaxis and adenylyl and guanylyl cyclases in response to folate during the early stages of development and to a late class of folate receptors (beta FAR) that have different specificities for pterins. G alpha 4 is preferentially expressed in cells randomly distributed within the aggregate that are a component of the anterior-like cell population, and it is not detectably expressed in prespore cells. Our results suggest that an endogenous factor, possibly a pterin, produced during multicellular development is a requisite signal for multicellular development, acting through G alpha 4. We propose that the G alpha 4-expressing cells function as a regulatory cell type controlling prespore cell fate, possibly in response to an endogenous pterin. Our results indicate that G alpha 4 and G alpha 2 have parallel functions in mediating cellular responses to folate (pterins) and cAMP, respectively.
Hadwiger
J A
JA
Department of Biology, University of California, San Diego, La Jolla 92093-0634.
Lee
S
S
Firtel
R A
RA
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D001708:Biopterins / Q000031:analogs & derivatives / Q000494:pharmacology; D002352:Carrier Proteins / Q000378:metabolism / Q000502:physiology*; D002455:Cell Division; D002633:Chemotaxis / Q000187:drug effects / Q000502:physiology; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D004023:Dictyostelium / Q000187:drug effects / Q000254:growth & development / Q000502:physiology*; D005455:Fluorescent Antibody Technique; D058973:Folate Receptors, GPI-Anchored; D005492:Folic Acid / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000096:biosynthesis / Q000378:metabolism*; D006162:Guanylate Cyclase / Q000378:metabolism; D046911:Macromolecular Substances; D019798:Neopterin; D015800:Protozoan Proteins; D011956:Receptors, Cell Surface / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled; D015398:Signal Transduction
D002352:Carrier Proteins; D058973:Folate Receptors, GPI-Anchored; D046911:Macromolecular Substances; D015800:Protozoan Proteins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; C090050:pterin receptor, Dictyostelium; D001708:Biopterins; D019798:Neopterin; D005492:Folic Acid; D000242:Cyclic AMP; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases; D006162:Guanylate Cyclase; D006152:Cyclic GMP