Glorin signaling during the multicellular development of social amoebae (SIGMOSA)

• Applicants: Professor Dr. Pierre Stallforth; Professor Dr. Thomas Winckler
• Subject Area: Metabolism, Biochemistry and Genetics of Microorganisms ; Parasitology and Biology of Tropical Infectious Disease Pathogens
• Term: from 2018 to 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 398377386

Dictyostelia are a group of soil-dwelling protists that live as single cells and feed on bacteria. Under certain environmental conditions such as food depletion, these single cells can enter a multicellular phase. Initial aggregation occurs by chemotactic movement through pulses or gradients of diffusible extracellular signal molecules known as ‘acrasins’. The term ‘social amoebae’ was specifically coined to emphasize that single cells in the multicellular organism differentiate and cooperate when forming a fruiting body in which dead stalk cells support dormant spores. These systems are thus exquisite model organisms to unravel fundamental aspects of the evolution and orchestration of multicellularity. The best-characterized acrasin is cyclic adenosine monophosphate (cAMP) that coordinates all phases of multicellular development in the model organism Dictyostelium discoideum. However, most species of social amoebae do not use cAMP to coordinate aggregation and seem to use the modified dipeptide glorin (N-propionyl-γ-L-glutamyl-L-δ-lactam-ethylester) that was first identified and isolated by John Bonner and co-workers as the acrasin of the social amoeba Polysphondylium violaceum. Glorin-based signaling seems to be the ancestral communication system used by social amoebae during aggregation, and several species have lost this system and replaced it by others such as cAMP-mediated signaling. Little is known about the signaling machinery of glorin-based communication. The aim of this project is to identify the glorin receptor and the enzyme(s) that hydrolytically inactivate glorin. The approach used in this proposal is an interdisciplinary combination of biochemical and chemical biology methods. In particular, we will make use of chemical probes (e.g. for photoaffinitylabeling) that will enable mass-spectrometry-based proteomic studies. Although multicellularity in social amoebae and ‘higher’ eukaryotes have evolved using different paths, a comparison of the cAMP- and glorin-based signaling systems in social amoebae will highlight fundamental aspects of intercellular communication required to establish and maintain multicellularity in eukaryotic organisms.

• DFG Programme: Research Grants