Chammas R, McCaffery J M, Klein A, Ito Y, Saucan L, Palade G, Farquhar M G, Varki A
Glycobiology Program, University of California, San Diego, Cancer Center, La Jolla 92093, USA.
Mol Biol Cell. 1996 Nov;7(11):1691-707. doi: 10.1091/mbc.7.11.1691.
The transfer of sialic acids (Sia) from CMP-sialic acid (CMP-Sia) to N-linked sugar chains is thought to occur as a final step in their biosynthesis in the trans portion of the Golgi apparatus. In some cell types such Sia residues can have O-acetyl groups added to them. We demonstrate here that rat hepatocytes express 9-O-acetylated Sias mainly at the plasma membranes of both apical (bile canalicular) and basolateral (sinusoidal) domains. Golgi fractions also contain 9-O-acetylated Sias on similar N-linked glycoproteins, indicating that O-acetylation may take place in the Golgi. We show here that CMP-Sia-FITC (with a fluorescein group attached to the Sia) is taken up by isolated intact Golgi compartments. In these preparations, Sia-FITC is transferred to endogenous glycoprotein acceptors and can be immunochemically detected in situ. Addition of unlabeled UDP-Gal enhances Sia-FITC incorporation, indicating a substantial overlap of beta-galactosyltransferase and sialyltransferase machineries. Moreover, the same glycoproteins that incorporate Sia-FITC also accept [3H]galactose from the donor UDP-[3H]Gal. In contrast, we demonstrate with three different approaches (double-labeling, immunoelectron microscopy, and addition of a diffusible exogenous acceptor) that sialyltransferase and O-acetyltransferase machineries are much more separated from one another. Thus, 9-O-acetylation occurs after the last point of Sia addition in the trans-Golgi network. Indeed, we show that 9-O-acetylated sialoglycoproteins are preferentially segregated into a subset of vesicular carriers that concentrate membrane-bound, but not secretory, proteins.
唾液酸(Sia)从CMP - 唾液酸(CMP - Sia)转移至N - 连接糖链的过程被认为是其在高尔基体反式部分生物合成的最后一步。在某些细胞类型中,此类Sia残基可被添加O - 乙酰基。我们在此证明,大鼠肝细胞主要在顶端(胆小管)和基底外侧(窦状隙)结构域的质膜上表达9 - O - 乙酰化的Sia。高尔基体组分在类似的N - 连接糖蛋白上也含有9 - O - 乙酰化的Sia,这表明O - 乙酰化可能发生在高尔基体中。我们在此表明,CMP - Sia - FITC(荧光素基团连接到Sia上)被分离的完整高尔基体区室摄取。在这些制剂中,Sia - FITC被转移至内源性糖蛋白受体,并可通过免疫化学方法原位检测。添加未标记的UDP - Gal可增强Sia - FITC的掺入,表明β - 半乳糖基转移酶和唾液酸转移酶机制存在大量重叠。此外,掺入Sia - FITC的相同糖蛋白也从供体UDP - [³H]Gal接受[³H]半乳糖。相反,我们用三种不同方法(双标记、免疫电子显微镜和添加可扩散的外源性受体)证明,唾液酸转移酶和O - 乙酰转移酶机制彼此之间的分隔更为明显。因此,9 - O - 乙酰化发生在反式高尔基体网络中Sia添加的最后一点之后。实际上,我们表明9 - O - 乙酰化的唾液糖蛋白优先被分选到一类囊泡载体中,这些载体富集膜结合蛋白而非分泌蛋白。