The signal peptide of the mouse mammary tumor virus Rem protein is released from the endoplasmic reticulum membrane and accumulates in nucleoli
The signal peptide of the mouse mammary tumor virus Rem protein is released from the endoplasmic reticulum membrane and accumulates in nucleoli
复制标题
DOI：
10.1074/jbc.m705712200
复制
发表时间：
2008-04-11
影响因子：
4.8
通讯作者：
Kapp, Katja
中科院分区：
文献类型：
--
作者：
Dultz, Elisa;Hildenbeutel, Markus;Kapp, Katja
N-末端信号序列介导内质网（ER）靶向和新生分泌和膜蛋白的插入，并且在大多数情况下，被信号肽酶切割。小鼠乳腺肿瘤病毒包膜蛋白及其可变剪接变异体Rem具有异常长的信号序列，其中含有核定位信号。尽管包膜蛋白被靶向ER、插入和糖基化，但Rem被描述为核蛋白。REM以及与切割的信号序列相同的截短形式已被证明作为含内含子转录物的核输出因子起作用。使用瞬时转染的细胞，我们发现Rem靶向ER，其中C-末端部分被易位和糖基化。信号序列被切除并积聚在核仁中。在无细胞的体外系统中，Rem信号肽的产生取决于微粒体膜的存在。在体外和细胞中，信号肽最初积累在膜中，随后释放到胞质溶胶中。这种释放不依赖于信号肽肽酶的加工，信号肽肽酶是一种膜内切割蛋白酶，可以介导信号肽片段从ER膜的释放。我们的研究提示了一种新的途径，通过该途径，信号肽可以从ER膜释放，以在不同的隔室中实现后靶向功能。
N-terminal signal sequences mediate endoplasmic reticulum (ER) targeting and insertion of nascent secretory and membrane proteins and are, in most cases, cleaved off by signal peptidase. The mouse mammary tumor virus envelope protein and its alternative splice variant Rem have an unusually long signal sequence, which contains a nuclear localization signal. Although the envelope protein is targeted to the ER, inserted, and glycosylated, Rem has been described as a nuclear protein. Rem as well as a truncated version identical to the cleaved signal sequence have been shown to function as nuclear export factors for intron-containing transcripts. Using transiently transfected cells, we found that Rem is targeted to the ER, where the C-terminal portion is translocated and glycosylated. The signal sequence is cleaved off and accumulates in nucleoli. In a cell-free in vitro system, the generation of the Rem signal peptide depends on the presence of microsomal membranes. In vitro and in cells, the signal peptide initially accumulates in the membrane and is subsequently released into the cytosol. This release does not depend on processing by signal peptide peptidase, an intramembrane cleaving protease that can mediate the liberation of signal peptide fragments from the ER membrane. Our study suggests a novel pathway by which a signal peptide can be released from the ER membrane to fulfill a post-targeting function in a different compartment.