The prokaryote messenger c-di-GMP triggers stalk cell differentiation in Dictyostelium

摘要

第二信使是将来自受体的信号中继到细胞内预rn定目标的小分子。Cyclic-di-GMP是细菌中一rn种普遍存在的第二信使，比如说在生物膜的形rn成中就是活跃的，但此前一直没有在真核细胞rn中被观察到。现在，zhi-hui Chen和PaulinernSchaap演示了c-di-GMP在一种真核生物中所rn起的作用。这种真核生物即“盘基网柄菌”，rn从演化上来讲是一种古老的社会性阿米巴(变rn形虫)，它已成为细胞和发育生物学上的一个rn模型体系。本文作者发现，人们长期寻找的、rn在阿米巴中诱导多细胞分化(柄形成)的信号rn即c-di-GMP。它的合成酶“双鸟苷酸环化酶”rn专门在子实体端部表达，柄细胞就是在那里rn分化的。%Cyclic di-(3':5')-guanosine monophosphate (c-di-GMP) is a major prokaryote signalling intermediate that is synthesized by diguanylate cyclases and triggers sessility and biofilm formation1'2. We detected the first eukaryote diguanylate cyclases in all major groups of Dictyostelia. On food depletion, Dictyostelium discoideum amoebas collect into aggregates, which first transform into migrating slugs and then into sessile fruiting structures3. These structures consist of a spherical spore mass that is supported by a column of stalk cells and a basal disk. A polyketide, DIF-1, which induces stalk-like cells in vitro, was isolated earlier4. However, its role in vivo proved recently to be restricted to basal disk formation5. Here we show that the Dictyostelium diguanylate cydase, DgcA, produces c-di-GMP as the morphogen responsible for stalk cell differentiation. Dictyostelium discoideum DgcA synthesized c-di-GMP in a GTP-dependent manner and was expressed at the slug tip, which is the site of stalk cell differentiation. Disruption of the DgcA gene blocked the transition from slug migration to fructification and the expression of stalk genes. Fructification and stalk formation were restored by exposing DgeA-null slugs to wild-type secretion products or to c-di-GMP. Moreover, c-di-GMP, but not cyclic di-(3':5')-adenosine monophosphate, induced stalk gene expression in dilute cell monolayers. Apart from identifying the long-elusive stalk-inducing morphogen, our work also identifies a role for c-di-GMP in eukaryotes.