Neisseria gonorrhoeae breaches the apical junction of polarized epithelial cells for transmigration by activating EGFR.
Neisseria gonorrhoeae breaches the apical junction of polarized epithelial cells for transmigration by activating EGFR.
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DOI：
10.1111/cmi.12099
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发表时间：
2013-06
影响因子：
3.4
通讯作者：
Song W
中科院分区：
文献类型：
--
作者：
Edwards VL;Wang LC;Dawson V;Stein DC;Song W
淋病奈瑟菌在女性生殖道宫颈内柱状上皮细胞的顶端表面引发感染。这些细胞通过在相邻细胞之间形成连续的顶端连接复合体来提供针对病原体的物理屏障。本研究探讨淋球菌（GC）与极化上皮细胞的相互作用。我们发现，在极化的子宫内膜和结肠上皮细胞，HEC-1-B和T84中，活性GC优先定位于细胞-细胞连接的顶端。在GC感染的细胞中，连续的顶端连接复合体被破坏，连接相关蛋白β-连环蛋白从顶端连接重新分布到细胞质和GC粘附位点;然而，总体细胞水平保持不变。连接蛋白的这种重新分布与顶端连接的“栅栏”功能的减少有关，但与其“门”功能无关。通过去除钙而破坏顶端连接增加GC穿过上皮单层的迁移。GC接种诱导表皮生长因子受体（EGFR）和β-连环蛋白的磷酸化，而EGFR激酶活性的抑制显著降低GC诱导的β-连环蛋白再分布和GC迁移。因此，淋球菌能够通过激活EGFR来削弱上皮细胞的顶端连接和极性，从而促进GC穿过上皮的迁移。
Neisseria gonorrhoeae initiates infection at the apical surface of columnar endocervical epithelial cells in the female reproductive tract. These cells provide a physical barrier against pathogens by forming continuous apical junctional complexes between neighbouring cells. This study examines the interaction of gonococci (GC) with polarized epithelial cells. We show that viable GC preferentially localize at the apical side of the cell–cell junction in polarized endometrial and colonic epithelial cells, HEC-1-B and T84. In GC-infected cells, continuous apical junctional complexes are disrupted, and the junction-associated protein β-catenin is redistributed from the apical junction to the cytoplasm and to GC adherent sites; however, overall cellular levels remain unchanged. This redistribution of junctional proteins is associated with a decrease in the ‘fence’ function of the apical junction but not its ‘gate’ function. Disruption of the apical junction by removing calcium increases GC transmigration across the epithelial monolayer. GC inoculation induces the phosphorylation of both epidermal growth factor receptor (EGFR) and β-catenin, while inhibition of EGFR kinase activity significantly reduces both GC-induced β-catenin redistribution and GC transmigration. Therefore, the gonococcus is capable of weakening the apical junction and polarity of epithelial cells by activating EGFR, which facilitates GC transmigration across the epithelium.
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影响因子：
56.9
作者：
Coureuil, Mathieu;Mikaty, Guillain;Nassif, Xavier
通讯作者：
Nassif, Xavier
影响因子：
3.2
作者：
BEROD, A;HARTMAN, BK;PUJOL, JF
通讯作者：
PUJOL, JF
影响因子：
5.5
作者：
Bertelsen, LS;Paesold, G;Barrett, KE
通讯作者：
Barrett, KE
影响因子：
3.4
作者：
Boyle, Erin C.;Brown, Nat F.;Finlay, B. Brett
通讯作者：
Finlay, B. Brett
影响因子：
3.1
作者：
DRAPER, DL;JAMES, JF;SWEET, RL
通讯作者：
SWEET, RL