Glorin signaling during the multicellular development of social amoebae
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 in gradients of diffusible extracellular signal molecules known as "acrasins". The term "social amoebae" was 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 organisms are exquisite models to unravel fundamental aspects of the evolution and orchestration of multicellularity.
The modified dipeptide glorin (N-propionyl-γ-L-glutamyl-L-δ-lactam-ethylester) was first isolated as the acrasin that regulates aggregation of the social amoeba Polysphondylium violaceum. The limited knowledge of the glorin-based acrasin system dates back approximately 30 years and is solely based on biochemical methods available at the time. In our work we combine biochemical, molecular biology, and chemical biology approaches to identify protein components of regulatory networks that regulate the early development of Polysphondylia.
Selected publications:
- D. Heinrich, R. Barnett, L. Tweedy, R. Insall, P. Stallforth & T. Winckler (2018). The chemoattractant glorin is inactivated by ester cleavage during early multicellular development of Polysphondylium pallidum. ACS Chem. Biol. 13, 1506-1513 (PubMedExternal link)
- R. Barnett, D. Raszkowski, T. Winckler & P. Stallforth (2017). Versatile synthesis of the signaling peptide glorin. Beilstein J. Org. Chem. 13, 247-250 (PubMedExternal link)
- A. Asghar, M. Groth, O. Siol, F. Gaube, C. Enzensperger, G. Glöckner & T. Winckler (2012). Developmental gene regulation by an ancient intercellular communication system in social amoebae. Protist 163, 25-37 (PubMedExternal link)