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.