Cell signaling by the type IV pili of pathogenic Nisseria
Cell signaling by the type IV pili of pathogenic Nisseria
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DOI：
10.1074/jbc.273.34.21777
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发表时间：
1998-08-21
影响因子：
4.8
通讯作者：
Jonsson, AB
中科院分区：
文献类型：
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作者：
Källström, H;Islam, MS;Jonsson, AB
淋病奈瑟菌和脑膜炎奈瑟菌是感染人类粘膜上皮的革兰氏阴性细菌病原体。 TV 型菌毛介导的这些细菌的粘附是感染建立的关键早期事件。在这项工作中，我们证明了 IV 型药丸将信号转导到真核宿主细胞中。纯化的贴壁药丸（而非低结合突变体的药丸）会引发靶上皮细胞中胞质游离钙 ([Ca2+](i)) 的增加，这是一种已知控制许多细胞反应的信号。 [Ca2+](i) 的增加被针对 CD46（一种假定的菌毛受体）的抗体阻断，表明该蛋白在信号转导中的作用。菌毛介导的附着受到宿主细胞胞内 Ca2+ 储存的耗尽的抑制，但不会被胞外 Ca2+ 的去除所抑制。此外，激酶抑制研究表明菌毛介导的粘附依赖于酪蛋白激酶 II。总之，这些数据揭示了 IV 型药丸的一个新功能，即诱导宿主细胞中的信号转导途径。
Neisseria gonorrhoeae and Neisseria meningitidis are Gram-negative bacterial pathogens that infect human mucosal epithelia. Type TV pilus-mediated adherence of these bacteria is a crucial early event for establishment of infection. In this work, we show that the type IV pill transduce a signal into the eucaryotic host cell. Purified adherent pill, but not pill from a low binding mutant, trigger an increase in the cytosolic free calcium ([Ca2+](i)) in target epithelial cells, a signal known to control many cellular responses. The [Ca2+](i) increase was blocked by antibodies against CD46, a putative pilus receptor, suggesting a role for this protein in signal transduction. Pilus-mediated attachment was inhibited by depletion of host cell intracellular Ca2+ stores but not by removal of extracellular Ca2+. Further, kinase inhibition studies showed that pilus-mediated adherence is dependent on casein kinase II. In summary, these data reveal a novel function of the type IV pill, namely induction of signal transduction pathways in host cells.