Dictyostelium discoideum chemotaxis is altered by hypoxia to orient streaming toward higher oxygen levels.

Abstract

BACKGROUND: Dictyostelium discoideum (Dd) exhibits a unique life cycle marked by its transition from single-cell amoeboid movement to multicellular development in response to environmental stimuli. While its chemotactic response to cyclic adenosine monophosphate (cAMP) has been extensively studied, experiments are usually carried out in a high oxygen (O2) environment (21% O2, also called normoxia) that might not reflect the natural condition for a soil amoeba as low O2 (hypoxia) is common underground. Our recent research has unveiled a novel phenomenon termed aerotaxis, wherein Dd cells migrate towards O2-rich environments under hypoxia. RESULTS: We tested Dd response when submitted to two different stress sources: starvation and hypoxia. While both stresses induced a motile response, namely chemotaxis and aerotaxis, we were able to decouple both types of responses to explore potential shared mechanisms. Importantly, aerotaxis appeared to be operated independently of known chemotactic pathways, demonstrating unique signaling pathways and cellular responses. Aerotaxis contributed to Dd developmental processes by letting cells escape from acute hypoxia. Even though chemotactic response could occur at < 2% O2, it did not lead to well organized or stable streaming. Furthermore, in an O2 gradient, aggregation centers for chemotactic response appeared preferentially at higher O2 levels. RT-qPCR analysis showed that hypoxia only slightly reduced the expression of genes required for chemotactic response, suggesting that the bias toward high O2 might occur at another level. Reoxygenation of cells that had been starved in hypoxic conditions for 18 h allowed rapid aggregation but required de novo protein synthesis. CONCLUSION: Aerotaxis and chemotaxis mechanisms do not interact directly. However, when cells are exposed to both starvation and hypoxia, both mechanisms can be combined to direct the migration of cells toward places with higher O2 levels. As hypoxia is frequent in the soil where Dd usually grows, formation of aggregation centers at or close to the soil surface, where O2 is abundant, will be advantageous. Low O2 levels do not preclude cells from participating in streaming but seem to reduce or delay their ability to produce stable aggregation centers, resulting in a bias favoring centers that form at higher O2 levels.