The number of the C-terminal transmembrane domains has the potency to specify subcellular localization of Sec22c.
The number of the C-terminal transmembrane domains has the potency to specify subcellular localization of Sec22c.
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DOI：
10.1016/j.bbrc.2017.04.071
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发表时间：
2017-05
影响因子：
3.1
通讯作者：
Yasunori Yamamoto;Chisato Yurugi;T. Sakisaka
中科院分区：
文献类型：
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作者：
Yasunori Yamamoto;Chisato Yurugi;T. Sakisaka
Sec 22 c是一种位于内质网（ER）的跨膜蛋白，参与调节囊泡在ER和高尔基体之间的转运。Sec 22 c具有通过改变C-末端跨膜结构域（TMD）的数目的选择性剪接产生的几种同种型。然而，剪接的生理意义仍然未知。在这里，我们表明，剪接异构体包含四个TMD出乎意料地本地化atcis高尔基体，而剪接异构体包含少于四个TMD本地化在ER。含有4个TMD的C-末端片段足以用于泡膜-高尔基体定位，并与ADP-核糖基化因子4（ARF 4）结合。ARF 4敲低和过表达的组成型活性突变体的ARF 4降低了C-末端片段和全长蛋白质的膜-高尔基定位，分别。这些结果表明，TMDs数量的剪接依赖性变化允许Sec 22 c与ARF 4合作调节亚细胞定位，这意味着Sec 22 c将在高尔基体以及ER发挥作用。
Sec22c has been characterized as an endoplasmic reticulum (ER)-localized transmembrane protein involved in regulation of the vesicle transport between the ER and the Golgi. Sec22c has several isoforms generated by alternative splicing that changes the number of the C-terminal transmembrane domains (TMDs). However, the physiological significance of the splicing remains unknown. Here we show that the splicing isoforms containing four TMDs unexpectedly localized atcis-Golgi, whereas the splicing isoforms containing less than four TMDs localized at the ER. The C-terminal fragment containing the four TMDs was sufficient for thecis-Golgi localization and bound to ADP-ribosylation factor 4 (ARF4). ARF4 knockdown and overexpression of a constitutively active mutant of ARF4 decreased thecis-Golgi localization of the C-terminal fragment and the full-length protein, respectively. These results indicate that the splicing-dependent changes in the number of TMDs allow Sec22c to regulate the subcellular localization in cooperation with ARF4, implying that Sec22c will function at the Golgi as well as the ER.