Subtilase cytotoxin cleaves newly synthesized BiP and blocks antibody secretion in B lymphocytes.
Subtilase cytotoxin cleaves newly synthesized BiP and blocks antibody secretion in B lymphocytes.
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DOI：
10.1084/jem.20090782
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发表时间：
2009-10-26
期刊：
影响因子：
--
通讯作者：
Ploegh HL
中科院分区：
文献类型：
--
作者：
Hu CC;Dougan SK;Winter SV;Paton AW;Paton JC;Ploegh HL
产志贺毒素大肠杆菌 (STEC) 使用枯草杆菌酶细胞毒素 (SubAB) 干扰适应性免疫。它对免疫球蛋白分泌的抑制既快速又深刻。 SubAB 有利于裂解新合成的免疫球蛋白重链结合蛋白 (BiP)，产生包含 BiP 底物结合结构域的 C 末端片段。在缺乏调节核苷酸结合结构域的情况下，SubAB 切割的 C 端 BiP 片段仍然与新合成的免疫球蛋白轻链紧密结合，导致轻链保留在内质网 (ER) 中。因此，免疫球蛋白被滞留在内质网中，使得经过 SubAB 处理的 B 细胞无法分泌抗体。 SubAB 的抑制作用对抗体分泌具有高度特异性，因为其他分泌蛋白（例如 IL-6）可以从 SubAB 处理的 B 细胞中正常释放。尽管 SubAB 也会在 HepG2 肝癌细胞中引起 BiP 裂解，但在暴露于 SubAB 的 HepG2 细胞中，（糖）蛋白的分泌继续有增无减。这种抗体分泌的特异性阻断是 STEC 免疫逃避的一种新方法。 SubAB 在 ER 中对新合成的 BiP 与“老化”BiP 的差异裂解提供了对相关 ER 区室结构的深入了解。
Shiga-toxigenic Escherichia coli (STEC) use subtilase cytotoxin (SubAB) to interfere with adaptive immunity. Its inhibition of immunoglobulin secretion is both rapid and profound. SubAB favors cleavage of the newly synthesized immunoglobulin heavy chain–binding protein (BiP) to yield a C-terminal fragment that contains BiP’s substrate-binding domain. In the absence of its regulatory nucleotide-binding domain, the SubAB-cleaved C-terminal BiP fragment remains tightly bound to newly synthesized immunoglobulin light chains, resulting in retention of light chains in the endoplasmic reticulum (ER). Immunoglobulins are thus detained in the ER, making impossible the secretion of antibodies by SubAB-treated B cells. The inhibitory effect of SubAB is highly specific for antibody secretion, because other secretory proteins such as IL-6 are released normally from SubAB-treated B cells. Although SubAB also causes BiP cleavage in HepG2 hepatoma cells, (glyco)protein secretion continues unabated in SubAB-exposed HepG2 cells. This specific block in antibody secretion is a novel means of immune evasion for STEC. The differential cleavage of newly synthesized versus “aged” BiP by SubAB in the ER provides insight into the architecture of the ER compartments involved.
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DOI：
10.1073/pnas.92.5.1764
发表时间：
1995-02-28
影响因子：
11.1
作者：
KNITTLER, MR;DIRKS, S;HAAS, IG
通讯作者：
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影响因子：
3.3
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影响因子：
64.8
作者：
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影响因子：
64.8
作者：
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影响因子：
3.4
作者：
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