Screening a series of sialyltransferases for possible BACE1 substrates
Screening a series of sialyltransferases for possible BACE1 substrates
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DOI：
10.1007/s10719-006-6671-x
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发表时间：
2006-07-01
影响因子：
3
通讯作者：
Hashimoto, Yasuhiro
中科院分区：
文献类型：
--
作者：
Kitazume, Shinobu;Tachida, Yuriko;Hashimoto, Yasuhiro
脑内淀粉样β肽（A β）沉积和神经元缠结是阿尔茨海默病（AD）发病机制的标志。BACE 1是一种膜结合天冬氨酸蛋白酶，可切割淀粉样前体蛋白（APP）产生A β，与引发该疾病的发病机制有关。我们以前报道，BACE 1也切割α 2，6-唾液酸转移酶（ST 6 Gal I）在高尔基体，并诱导其分泌的细胞。由于大多数糖基转移酶显示高尔基体定位，并且其中许多被切割并从细胞分泌，我们假设其他糖基转移酶也可能是BACE 1底物。在这里，我们集中在一系列的唾液酸转移酶作为BACE 1底物的候选人。我们发现BACE 1在体外切割聚唾液酸转移酶ST 8 Sia IV（PST）。我们进一步发现，BACE 1在COS细胞中的过表达增强了ST 3Gal I、II、III和IV的分泌，尽管这些唾液酸转移酶在体外不被BACE 1切割。这些结果表明，BACE 1的表达不仅通过直接切割糖基转移酶，而且还通过一些其他机制修改糖基转移酶的分泌来影响糖基化。
Deposition of amyloid beta-peptide (A beta) and neurofibrillary tangles in the brain are hallmarks of Alzheimer's disease (AD) pathogenesis. BACE1, a membrane-bound aspartic protease that cleaves amyloid precursor protein (APP) to produce A beta, has been implicated in triggering the pathogenesis of the disease. We previously reported that BACE1 also cleaved alpha 2,6-sialyltransferase (ST6Gal I) in the Golgi apparatus and induced its secretion from the cell. Since most glycosyltransferases show Golgi localization and many of these are cleaved and secreted from the cell, we hypothesized that other glycosyltransferases may also be BACE1 substrates. Here, we focused on a series of sialyltransferases as candidates for BACE1 substrates. We found that BACE1 cleaved polysialyltransferase ST8Sia IV (PST) in vitro. We further found that BACE1 overexpression in COS cells enhanced the secretion of ST3Gal I, II, III and IV, although these sialyltransferases were not cleaved by BACE1 in vitro. These results suggest that BACE1 expression affects glycosylation not only by directly cleaving glycosyltransferases but also by modifying the secretion of glycosyltransferases via some other mechanisms.