Secreting and Sensing the Same Molecule Allows Cells to Achieve Versatile Social Behaviors

The Message in the Medium

What is the point of autocrine signaling in which a cell produces a signal that activates receptors on its own cell surface? An internal signal seems simpler, unless there is value to allowing neighboring cells to know what other cells are up to. Youk and Lim (p. [Related article:]10.1126/science.1242782 ; see the Perspective by [Related article:] Lee and You ) explored the broad range of signaling outcomes that can result in a system in which some yeast cells could secrete and sense a signal whereas others could only sense signals from their neighbors. The cells were engineered so that the response of the two cell types could be distinguished from one another. Experiments and mathematical modeling showed that depending on how circuits were constructed—for example, how much receptor was present, how the signal molecule was degraded, the presence of feedback, the density of the cell culture, and so on—a range of behaviors was possible: Some conditions favored activation of one type of cell over another. Others altered the timing or consistency of the response within a population. The principles revealed could also be used in other biological contexts or in the design of synthetic biological cell systems with desired regulatory properties.

Abstract

The etiquette of yeast cells that secrete signals that influence themselves and their neighbors is explored. [Also see Perspective by [Related article:]Lee and You ]

Abstract

Cells that secrete and sense the same signaling molecule are ubiquitous. To uncover the functional capabilities of the core “secrete-and-sense” circuit motif shared by these cells, we engineered yeast to secrete and sense the mating pheromone. Perturbing each circuit element revealed parameters that control the degree to which the cell communicated with itself versus with its neighbors. This tunable interplay of self-communication and neighbor communication enables cells to span a diverse repertoire of cellular behaviors. These include a cell being asocial by responding only to itself and social through quorum sensing, and an isogenic population of cells splitting into social and asocial subpopulations. A mathematical model explained these behaviors. The versatility of the secrete-and-sense circuit motif may explain its recurrence across species.