Glycosylphosphatidylinositol mannosyltransferase II is the rate-limiting enzyme in glycosylphosphatidylinositol biosynthesis under limited dolichol-phosphate mannose availability
Glycosylphosphatidylinositol mannosyltransferase II is the rate-limiting enzyme in glycosylphosphatidylinositol biosynthesis under limited dolichol-phosphate mannose availability
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DOI：
10.1093/jb/mvt045
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发表时间：
2013-09-01
影响因子：
2.7
通讯作者：
Kinoshita, Taroh
中科院分区：
文献类型：
--
作者：
Hirata, Tetsuya;Fujita, Morihisa;Kinoshita, Taroh
尽管参与糖基磷脂酰肌醇（GPI）生物合成的基因已被很好地表征，但GPI生物合成的调控仍不清楚。我们分离并表征了一种突变细胞系，其显示CD 59的表面表达降低和GPI中间体的积累。突变细胞系在MPDU 1中部分缺陷，MPDU 1编码利用多萜醇-磷酸甘露糖所需的蛋白质。过表达的PIGV，它编码GPI甘露糖转移酶II，恢复了表面表达的CD 59和正常的积累GPI中间体的突变细胞。在所有已知的GPI生物合成途径相关基因中，只有PIGV具有这种抑制活性。但PIGV不能恢复MPDU 1突变引起的N-糖基化异常。我们的研究结果表明，GPI甘露糖基转移酶II是有限的甘露醇磷酸甘露糖的可用性下GPI生物合成的限速酶。
Although the genes involved in the biosynthesis of glycosylphosphatidylinositol (GPI) are well characterized, the regulation of GPI biosynthesis remains unclear. We isolated and characterized a mutant cell line showing decreased surface expression of CD59 and the accumulation of GPI intermediates. The mutant cell line was partially defective in MPDU1, which encodes a protein required for the utilization of dolichol-phosphate mannose. Overexpression of PIGV, which encodes GPI mannosyltransferase II, restored the surface expression of CD59 and normalized the accumulation of GPI intermediates in the mutant cells. Among all known genes involved in GPI biosynthetic pathway, only PIGV had such suppressive activity. PIGV, however, did not restore the abnormality of N-glycosylation caused by MPDU1 mutation. Our results suggest that GPI mannosyltransferase II is the rate-limiting enzyme in GPI biosynthesis under limited dolichol-phosphate mannose availability.