Department of Physics, University of California San Diego, La Jolla, CA 92093.
Department of Biology, Texas A&M University, College Station, TX 77843.
Proc Natl Acad Sci U S A. 2021 Feb 9;118(6). doi: 10.1073/pnas.2008126118.
Chemotaxis, the guided motion of cells by chemical gradients, plays a crucial role in many biological processes. In the social amoeba , chemotaxis is critical for the formation of cell aggregates during starvation. The cells in these aggregates generate a pulse of the chemoattractant, cyclic adenosine 3',5'-monophosphate (cAMP), every 6 min to 10 min, resulting in surrounding cells moving toward the aggregate. In addition to periodic pulses of cAMP, the cells also secrete phosphodiesterase (PDE), which degrades cAMP and prevents the accumulation of the chemoattractant. Here we show that small aggregates of can disperse, with cells moving away from instead of toward the aggregate. This surprising behavior often exhibited oscillatory cycles of motion toward and away from the aggregate. Furthermore, the onset of outward cell motion was associated with a doubling of the cAMP signaling period. Computational modeling suggests that this dispersal arises from a competition between secreted cAMP and PDE, creating a cAMP gradient that is directed away from the aggregate, resulting in outward cell motion. The model was able to predict the effect of PDE inhibition as well as global addition of exogenous PDE, and these predictions were subsequently verified in experiments. These results suggest that localized degradation of a chemoattractant is a mechanism for morphogenesis.
趋化性，即细胞在化学梯度引导下的定向运动，在许多生物学过程中起着至关重要的作用。在社会性粘菌中，趋化性对于饥饿时细胞聚集体的形成至关重要。这些聚集体中的细胞每隔 6 分钟到 10 分钟就会产生一波化学引诱剂环腺苷酸（cAMP），导致周围的细胞向聚集体移动。除了周期性的 cAMP 脉冲外，细胞还分泌磷酸二酯酶（PDE），后者降解 cAMP 并防止化学引诱剂的积累。本文展示了小的聚集体能够分散，细胞会远离聚集体而不是向聚集体移动。这种令人惊讶的行为通常表现为向聚集体和远离聚集体的运动呈振荡循环。此外，细胞向外运动的开始与 cAMP 信号传递周期的两倍增加有关。计算模型表明，这种分散是由分泌的 cAMP 和 PDE 之间的竞争引起的，从而产生了一个远离聚集体的 cAMP 梯度，导致细胞向外运动。该模型能够预测 PDE 抑制和外源 PDE 整体添加的效果，这些预测随后在实验中得到了验证。这些结果表明，局部降解化学引诱剂是形态发生的一种机制。
