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 signaling pathway that is essential for multicellular development in Dictyostelium. G(alpha)4 is developme ntally regulated, is essential for proper morphogenesis and spore prod uction, 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 o f 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 detect ably expressed in prespore cells. Our results suggest that an endogeno us factor, possibly a pterin, produced during multicellular developmen t 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 res ponse 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.