Eukaryotic-like signaling and gene regulation in a prokaryote that undergoes multicellular development

Abstract

How cell–cell signaling coordinates cell movement, gene expression, and differentiation during the development of multicellular organisms is a fundamental question. At the molecular level, the answer is complex, even in the simplest cases. Myxococcus xanthus is one of the simplest organisms that undergo development to produce a multicellular structure of uniform size and shape. Cells of this bacterium sense nutrient limitation and alter their gliding movements to produce mounds (Fig. 1). Within these nascent fruiting bodies, cells differentiate into spores. Driving this developmental process is a program of gene expression that is temporally and spatially regulated by intracellular and extracellular signals. Are the typical prokaryotic signaling and gene regulatory mechanisms sufficient for multicellular development of M. xanthus ? Previous work has indicated that eukaryotic-like mechanisms play a role. The work of Jelsbak et al . (1) in this issue of PNAS extends this observation by describing a group of 12 M. xanthus genes that seem to encode enhancer-binding proteins (EBPs) with a forkhead-associated (FHA) domain. The authors show that the FHA domain of one of the EBPs is required for normal development. Because FHA domains interact with phosphothreonine residues, the results suggest a crucial link to eukaryotic-like Ser/Thr protein kinases (STPKs), which are abundant in M. xanthus . Fig. 1. Cartoon depicting starved M . xanthus cells forming a mound, then a fruiting body, which would contain ≈105 spores. Bacterial EBPs derive their name from the fact that they activate transcription by σ54-RNA polymerase (σ54-RNAP) in much the same way some EBPs activate transcription in eukaryotes. σ54-RNAP requires interaction with an EBP to form the transcriptionally competent open promoter complex. Bacterial EBPs bind to DNA enhancer elements typically located 70–150 bp upstream of the transcription start site (reviewed in ref. 2). Bending of DNA allows …