gdt1, a new signal transduction component for negative regulation of the growth-differentiation transition in Dictyostelium discoideum

Discoidin I expression was used as a marker to screen for mutants affected in the growth differentiation transition (GDT) of Dictyostelium. By REMI mu tagenesis we have isolated mutant 2-9, an overexpressor of discoidin I. It displays normal morphogenesis but shows premature entry into the developmen tal cycle. The disrupted gene was denominated gdt1. The mutant phenotype wa s reconstructed by disruptions in different parts of the gene, suggesting t hat all had a complete loss of function. gdt1 was expressed in growing cell s; the levels of protein and mRNA appear to increase with cell density and rapidly decrease with the onset of development. gdt1 encodes a 175-kDa prot ein with four putative transmembrane domains. In the C terminus, the derive d amino acid sequence displays some similarity to the catalytic domain of p rotein kinases. Mixing experiments demonstrate that the gdt1(-) phenotype i s eel autonomous. Prestarvation factor is secreted at wild-type levels. The response to folate, a negative regulator of discoidin expression, was not impaired in gdt1 mutants. Cells that lack the G protein alpha 2 display a l oss of discoidin expression and do not aggregate. gdt1(-)/G alpha 2(-) doub le mutants show no aggregation but strong discoidin expression This suggest s that gdt1 is a negative regulator of the GDT downstream of or in a parall el pathway to G alpha 2.