Rer1p, a retrieval receptor for ER membrane proteins, recognizes transmembrane domains in multiple modes
Rer1p, a retrieval receptor for ER membrane proteins, recognizes transmembrane domains in multiple modes
复制标题
DOI：
10.1091/mbc.e02-12-0777
复制
发表时间：
2003-09-01
影响因子：
3.3
通讯作者：
Nakano, A
中科院分区：
文献类型：
--
作者：
Sato, K;Sato, M;Nakano, A
酵母高尔基体膜蛋白Rer1p对于将多种内质网（ER）膜蛋白（如Sec12p和Sec71p）回收到内质网是必需的。我们在此证明，Sec71p（一种III型膜蛋白）的跨膜结构域（TMD）包含一个内质网定位信号，这是被Rer1p物理识别所必需的。Sec71TMD - GFP融合蛋白能被Rer1p有效地回收到内质网。这个TMD信号的结构特征是位于高度疏水核心序列两侧的极性残基的空间位置，而非TMD的全长。在Rer1p方面，第4个TMD中的Tyr152残基对于Sec12p的识别很重要，但对于Sec71p不重要，这表明Rer1p与其配体至少以两种模式相互作用。在Δrer1突变体细胞中表达的Sec71TMD - GFP通过多囊泡体（MVB）分选途径从内质网错误定位到液泡腔。在这种情况下，不仅Sec71TMD中极性残基的存在，而且TMD的长度对于MVB分选都至关重要。因此，依赖于Rer1p的内质网回收和晚期内体中的MVB分选都关注TMD中的极性残基，但方式不同。
The yeast Golgi membrane protein Rer1p is required for the retrieval of various endoplasmic reticulum (ER) membrane proteins such as Sec12p and Sec71p to the ER. We demonstrate here that the transmembrane domain (TMD) of Sec71p, a type-III membrane protein, contains an ER localization signal, which is required for physical recognition by Rer1p. The Sec71TMD-GFP fusion protein is efficiently retrieved to the ER by Rer1p. The structural feature of this TMD signal turns out to be the spatial location of polar residues flanking the highly hydrophobic core sequence but not the whole length of the TMD. On the Rer1p side, Tyr152 residue in the 4th TMD is important for the recognition of Sec12p but not Sec71p, suggesting that Rer1p interacts with its ligands at least in two modes. Sec71TMD-GFP expressed in the Deltarer1 mutant cells is mislocalized from the ER to the lumen of vacuoles via the multivesicular body (MVB) sorting pathway. In this case, not only the presence of polar residues in the Sec71TMD but also the length of the TMD is critical for the MVB sorting. Thus, the Rer1p-dependent ER retrieval and the MVB sorting in late endosomes both watch polar residues in the TMD but in a different manner.