N-glycosylation of ß4 integrin controls the adhesion and motility of keratinocytes.
N-glycosylation of ß4 integrin controls the adhesion and motility of keratinocytes.
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DOI：
10.1371/journal.pone.0027084
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Gu J
中科院分区：
文献类型：
--
作者：
Kariya Y;Gu J
α-6？4整合素是半桥粒的重要组成部分，在伤口愈合和肿瘤侵袭过程中调节细胞迁移。为了阐明N-糖基化对整合素的作用，我们通过野生型或N-糖基化缺陷的整合素(Δ)在整合素缺失的角质形成细胞中的重新表达，研究了角质形成细胞的黏附和迁移。β4整合素的N-糖基化不是与α6整合素形成异二聚体及其在细胞表面表达所必需的，但N-糖基化是整合素介导的细胞黏附和迁移所必需的。随着膜微区内Δ-4整合素表达的减少，细胞内AKT和ERK活化信号减弱。在ΔNü4整合素表达细胞中，强制交联型整合素可以挽救野生型整合素表达细胞中ERK活性的降低，其程度与野生型整合素表达细胞类似。令人惊讶的是，与表达野生型整合素的细胞相比，表达表皮生长因子受体的细胞的N-糖链结构发生了变化，并诱导了表皮生长因子受体与整合素之间更强的关联。在表达ΔNü4整合素的细胞中，观察到了表皮生长因子受体的N-糖链结构的改变。这些结果清楚地表明，整合素上的N-糖基化允许在细胞表面形成适当的复合体，从而在角质形成细胞的功能中发挥重要作用。
α6ß4 integrin is an essential component of hemidesmosomes and modulates cell migration in wound healing and cancer invasion. To elucidate the role of N-glycosylation on ß4 integrin, we investigated keratinocyte adhesion and migration through the re-expression of wild-type or N-glycosylation-defective ß4 integrin (ΔNß4) in ß4 integrin null keratinocytes. N-glycosylation of ß4 integrin was not essential for the heterodimer formation of ß4 integrin with α6 integrin and its expression on a cell surface, but N-glycosylation was required for integrin-mediated cell adhesion and migration. Concomitantly with the reduction of ß4 integrin in the membrane microdomain, the intracellular signals of Akt and ERK activation were decreased in cells expressing ΔNß4 integrin. Forced cross-linking of ß4 integrin rescued the decreased ERK activation in ΔNß4 integrin-expressing cells to a similar extent in wild-type ß4 integrin-expressing cells. Surprisingly, compared with cells expressing wild-type ß4 integrin, an alternation in N-glycan structures expressed on epidermal growth factor receptor (EGFR), and the induction of a stronger association between EGFR and ß4 integrin were observed in ΔNß4 integrin-expressing cells. These results clearly demonstrated that N-glycosylation on ß4 integrin plays an essential role in keratinocyte cellular function by allowing the appropriate complex formation on cell surfaces.
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DOI：
10.1083/jcb.153.3.465
发表时间：
2001-04-30
期刊：
The Journal of cell biology
影响因子：
--
作者：
Hintermann E;Bilban M;Sharabi A;Quaranta V
通讯作者：
Quaranta V
影响因子：
4.8
作者：
Nguyen, BP;Ren, XD;Carter, WG
通讯作者：
Carter, WG
影响因子：
3.3
作者：
Kim, Hong Im;Huang, Huang;Chung, Jun
通讯作者：
Chung, Jun
影响因子：
11.4
作者：
Mainiero, F;Murgia, C;Giancotti, FG
通讯作者：
Giancotti, FG
影响因子：
4.8
作者：
Kariya, Yoshinobu;Kawamura, Chihiro;Gu, Jianguo
通讯作者：
Gu, Jianguo