The NH2-Terminal transmembrane and lumenal domains of LGP85 are needed for the formation of enlarged endosomes/lysosomes
The NH2-Terminal transmembrane and lumenal domains of LGP85 are needed for the formation of enlarged endosomes/lysosomes
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DOI：
10.1111/j.1600-0854.2005.00325.x
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发表时间：
2005-10-01
期刊：
影响因子：
4.5
通讯作者：
Tanaka, Y
中科院分区：
文献类型：
--
作者：
Kuronita, T;Hatano, T;Tanaka, Y
LGP 85是具有III型拓扑结构的溶酶体膜蛋白，并且也被称为蛋白质的CD 36超家族的成员，例如CD 36和清道夫受体BI（SR-BI）。我们最近已经证明，LGP 85在各种哺乳动物细胞系中的过表达导致内体/溶酶体室（ELC）的扩大。使用嵌合体和缺失突变体，我们在这里表明，LGP 85的内腔区域是必要的，但不是足够的，ELC的发展。扩大ELC的有效形成在很大程度上取决于前面的NH 2-末端跨膜段的存在。内腔结构域内的缺失突变体的分析进一步揭示了NH 2-末端跨膜近端内腔区域的需求，与SR-BI具有高序列相似性以扩大ELC。这些结果表明，通过与跨膜结构域的连接，LGP 85的NH 2-末端跨膜近端内腔结构域与内体/溶酶体膜的内小叶的相互作用是调节内体/溶酶体膜运输的重要决定因素。有趣的是，虽然NH 2-末端跨膜结构域本身不足以扩大ELC，但它似乎是将LGP 85从trans-Golgi网络直接靶向晚期内体/溶酶体所必需的。总之，这些结果表明LGP 85的不同结构域参与ELC的靶向、生物发生和维持。
LGP85 is a lysosomal membrane protein possessing a type III topology and is also known as a member of the CD36 superfamily of proteins, such as CD36 and the scavenger-receptor BI (SR-BI). We have recently demonstrated that overexpression of LGP85 in various mammalian cell lines causes the enlargement of endosomal/lysosomal compartments (ELCs). Using chimeras and deletion mutants, we show here that the lumenal region of LGP85 is necessary, but not sufficient, for the development of ELCs. Effective formation of enlarged ELC was largely dependent on the presence of a preceding NH2-terminal transmembrane segment. Analyses of deletion mutants within the lumenal domain further revealed a requirement of the NH2-terminal transmembrane proximal lumenal region, with high sequence similarity with SR-BI for the enlargement of ELC. These results suggest that an interaction of the NH2-terminal transmembrane proximal lumenal domain of LGP85 with the inner leaflet of endosomal/lysosomal membranes through the connection with the transmembrane domain is an essential determinant for the regulation of endosomal/lysosomal membrane traffic. Interestingly, although the NH2-terminal transmembrane domain itself was not sufficient for the enlargement of ELCs, it appeared to be required for direct targeting of LGP85 from the trans-Golgi network to late endosomes/lysosomes. Taken together, these results indicate the involvement of distinct domain of LGP85 in the targeting to, and biogenesis and maintenance of, ELC.