Identification of the C-signal, a contact-dependent morphogen coordinating multiple developmental responses in Myxococcus xanthus

Identification of the C-signal, a contact-dependent morphogen coordinating multiple developmental responses in Myxococcus xanthus
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DOI:
10.1101/gad.274203
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发表时间:
2003-09-01
影响因子:
10.5
通讯作者:
Sogaard-Andersen, L
Sogaard-Andersen, L
中科院分区:
生物学1区
文献类型:
--
作者:
Lobedanz, S;Sogaard-Andersen, L

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黄色粘球菌中依赖接触的胞外C信号形态原的调节积累确保了子实体形成过程中多细胞形态发生和细胞分化的时空协调。C信号的合成依赖于CsgA基因。CsgA蛋白以两种形式存在,即与短链乙醇脱氢酶同源的全长25-kD蛋白(P25)和17-kD蛋白(P17)。C-信号的分子性质仍然难以捉摸。在这里,我们证明了p25和p17与外膜相关,p17与黄色微囊藻细胞的C-信号活性相互作用。P17对应于p25的C-末端部分。缺少N末端辅酶结合口袋的重组p17蛋白在体外不能与NAD(+)结合,具有C信号活性。这些数据提供了证据,证明p17是C信号中的活性物种,并且p17不作为短链酒精脱氢酶来产生C信号。我们进一步提供的证据表明,p17是通过丝氨酸蛋白酶对p25进行N端蛋白分解而合成的。与其他细菌信号分子相比,p17在大小和细胞表面结合方面是不寻常的。在这些方面,C-Signal在功能上类似于真核信号蛋白。
The regulated accumulation of the contact-dependent extracellular C-signal morphogen in the bacterium Myxococcus xanthus ensures the temporal and spatial coordination of multicellular morphogenesis and cellular differentiation during fruiting body formation. Synthesis of the C-signal depends on the csgA gene. The CsgA protein exists in two forms, the full-length 25-kD protein (p25), which is homologous to short-chain alcohol dehydrogenases, and a 17-kD protein (p17). The molecular nature of the C-signal has remained elusive. Here we show that p25 and p17 are associated with the outer membrane and that p17 copurifies with C-signal activity from M. xanthus cells. p17 corresponds to the C-terminal part of p25. A recombinant p17 protein, which lacks the N-terminal coenzyme binding pocket and which fails to bind NAD(+) in vitro, has C-signal activity. These data provide evidence that p17 is the active species in C-signaling and that p17 does not act as a short-chain alcohol dehydrogenase to generate the C-signal. We further provide evidence that p17 is synthesized by N-terminal proteolytic processing of p25 by a serine protease. Compared to other bacterial signaling molecules, p17 is unusual with respect to size and cell-surface association. In these regards, C-signal is functionally analogous to eukaryotic signaling proteins.