Intercellular C-signaling in Myxococcus xanthus involves a branched signal transduction pathway.

Abstract

C-factor, the product of the csgA gene, is a cell-surface associated short-range intercellular signaling protein in Myxococcus xanthus. C-factor is required for at least four responses during starvation-induced fruiting body morphogenesis: rippling, aggregation, sporulation, and full expression of the csgA gene, all of which fail in a csgA mutant. To analyze the C-factor signaling pathway, eight Tn5 lac insertion mutants that began but failed to complete fruiting body aggregation were characterized. Seven of the insertions identified genes whose products function in the csgA signaling pathway. The seven mutants were differentially deficient in the C-factor responses, and could be divided into two classes on the basis of those differences. On one hand, the four mutants in class I were deficient in rippling and aggregation, but sporulated and produced C-factor at wild-type levels. The Tn5 lac insertions in the class I mutants mapped to the frz locus, which encodes a signal transduction system that controls the frequency of single cell reversals. On the other hand, mutants carrying any of the three closely linked class II Tn5 lac insertions had deficiencies in all four C-factor responses. Because the sporulation defect in the class 11 mutants is cell autonomous, the data suggest that the primary defect in these mutants is an inability to respond to the C-factor signal. All the data can be explained by a model in which the first part of the C-factor signaling pathway is common to all four C-factor-dependent responses. The genes identified by the class 11 insertions would function in the common part. Downstream of class II, the pathway branches. One branch includes the frz genes and leads to aggregation and rippling; the second branch leads to sporulation and controls the level of csgA gene expression. This model was confirmed in epistasis tests with characterized frz mutations, a csgA null mutation, and a class II mutation.