Okamoto Aya, Morinaga Takao, Yamaguchi Noritaka, Yamaguchi Naoto
Laboratory of Molecular Cell Biology, Graduate School of Pharmaceutical Sciences, Chiba University.
Division of Pathology and Cell Therapy, Chiba Cancer Center Research Institute.
Biol Pharm Bull. 2018;41(1):142-146. doi: 10.1248/bpb.b17-00681.
Src-family tyrosine kinases, classified as cytosolic enzymes, have crucial roles in regulating cell proliferation, differentiation, migration and cell-shape changes. Newly synthesized Lyn, a member of Src-family kinases, is biosynthetically accumulated at the cytoplasmic face of caveolin-containing Golgi membranes via posttranslational lipid modifications and then transported to the plasma membrane. However, the precise intra-Golgi localization of Lyn remains elusive. By means of a 19°C block-release technique and short-term brefeldin A treatment, we show here that the distribution of Lyn is not monotonously spread within the Golgi but selectively intensified in two distinct membrane compartments: giantin- and caveolin-positive membranes and trans-Golgi network protein (TGN)46-positive but caveolin-negative membranes. Furthermore, Lyn exits the Golgi from the caveolin-positive cis-Golgi cisternae or the caveolin-negative trans-Golgi network. These results suggest that Lyn moves apart from caveolin, a secretory protein, within the Golgi during Lyn's trafficking to the plasma membrane.
Src家族酪氨酸激酶属于胞质酶,在调节细胞增殖、分化、迁移和细胞形态变化中起关键作用。新合成的Lyn是Src家族激酶的成员,通过翻译后脂质修饰在含小窝蛋白的高尔基体膜的胞质面进行生物合成积累,然后转运到质膜。然而,Lyn在高尔基体中的精确定位仍然不清楚。通过19°C阻断释放技术和短期布雷菲德菌素A处理,我们在此表明Lyn的分布在高尔基体中不是单调扩散的,而是在两个不同的膜区室中选择性增强:巨蛋白和小窝蛋白阳性膜以及反式高尔基体网络蛋白(TGN)46阳性但小窝蛋白阴性膜。此外,Lyn从含小窝蛋白的顺式高尔基体潴泡或小窝蛋白阴性的反式高尔基体网络离开高尔基体。这些结果表明,在Lyn转运到质膜的过程中,Lyn在高尔基体中与分泌蛋白小窝蛋白分离。