The 3'UTR of the α6 integrin message regulates localization of α6β4 integrin heterodimers.
The 3'UTR of the α6 integrin message regulates localization of α6β4 integrin heterodimers.
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α6 整合素消息的 3UTR 调节 α6β4 整合素异二聚体的定位。
DOI：
10.1016/j.bbrc.2019.03.116
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发表时间：
2019
影响因子：
3.1
通讯作者：
Jones,JonathanCR
中科院分区：
文献类型：
--
作者：
Woychek,Alexandra;Kligys,Kristina;Hopkinson,SusanB;Jones,JonathanCR
α6β4整合素异二聚体是半桥粒（HD）和HD相关结构的重要组成部分，其将上皮细胞粘附到下层细胞外基质。本研究旨在探讨α6β4整合素3′非翻译区（UTR）在α6β4整合素定位中的重要性。为此，A549细胞（一种II型肺泡细胞系）和永生化的人表皮角质形成细胞（iHEK）用编码完整α6整联蛋白（含或不含其3′UTR部分）的腺病毒感染。在感染的A549细胞中，我们检测到含有腺病毒产物的α6β4整合素异二聚体，而不管α6整合素3′UTR是否存在。然而，只有那些其信息包含α6整合素3′UTR的碱基4770-5633的α6整合素蛋白质靶向基质粘附位点。此外，A549细胞中全长α6整联蛋白3′UTR（减去编码序列）的过表达破坏了内源性α6β4整联蛋白异二聚体的定位。在用相同的腺病毒感染iHEK后，诱导的α6整联蛋白定位于HD，而不管其信息是否具有3′UTR。与此形成鲜明对比的是，在α6整联蛋白耗尽的iHEK中，仅使用编码序列通过腺病毒转导恢复α6整联蛋白表达导致α6整联蛋白优先形成α6β1而不是α6β4整联蛋白异二聚体。α6β4整合素仅在3′UTR编码α6整合素编码序列的腺病毒感染后的敲除细胞中观察到。总之，我们的数据表明，α6整合素3′UTR是α6β4整合素异二聚体组装和在细胞-基质粘附位点掺入的关键调节因子。
The α6β4 integrin heterodimer is an essential component of hemidesmosomes (HDs) and HD-related structures, which adhere epithelial cells to the underlying extracellular matrix. In this study, we focused on the importance of the α6 integrin 3′ untranslated region (UTR) in α6β4 integrin localization. To do so, A549 cells (a type II lung alveolar cell line) and immortalized human epidermal keratinocytes (iHEK) were infected with adenovirus encoding the entire α6 integrin protein with or without portions of its 3′UTR. In infected A549 cells, we detected α6β4 integrin heterodimers containing the product of the adenovirus, regardless of whether the α6 integrin 3′UTR was present. However, only those α6 integrin proteins whose messages contained bases 4770–5633 of the α6 integrin 3′UTR were targeted to matrix adhesion sites. Moreover, overexpression of the full length α6 integrin 3′UTR, minus the coding sequence, in A549 cells disrupts the localization of endogenous α6β4 integrin heterodimers. Following infection of iHEKs with the same adenovirus, the induced α6 integrin protein localizes to HDs regardless of whether its message possessed a 3′UTR. In sharp contrast, in α6 integrin depleted iHEKs, restoring α6 integrin expression using the coding sequence alone via adenoviral transduction resulted in α6 integrin preferentially forming α6β1 rather than α6β4 integrin heterodimers. α6β4 integrin was only observed in knocked down cells following infection of adenovirus encoding the α6 integrin coding sequence with its 3′UTR. In summary, our data indicate that the α6 integrin 3′UTR is a key regulator of α6β4 integrin heterodimer assembly and incorporation at sites of cell-matrix adhesion.