Sumida Mizuki, Hane Masaya, Yabe Uichiro, Shimoda Yasushi, Pearce Oliver M T, Kiso Makoto, Miyagi Taeko, Sawada Makoto, Varki Ajit, Kitajima Ken, Sato Chihiro
From the Bioscience and Biotechnology Center and School of Bioagricultural Sciences, Nagoya University, Nagoya, 464-8601, Japan.
Department of Bioengineering, Nagaoka University of Technology, 1603-1 Kamitomiokamachi, Nagaoka 940-2188 Japan.
J Biol Chem. 2015 May 22;290(21):13202-14. doi: 10.1074/jbc.M115.638759. Epub 2015 Mar 6.
As acidic glycocalyx on primary mouse microglial cells and a mouse microglial cell line Ra2, expression of polysialic acid (polySia/PSA), a polymer of the sialic acid Neu5Ac (N-acetylneuraminic acid), was demonstrated. PolySia is known to modulate cell adhesion, migration, and localization of neurotrophins mainly on neural cells. PolySia on Ra2 cells disappeared very rapidly after an inflammatory stimulus. Results of knockdown and inhibitor studies indicated that rapid surface clearance of polySia was achieved by secretion of endogenous sialidase Neu1 as an exovesicular component. Neu1-mediated polySia turnover was accompanied by the release of brain-derived neurotrophic factor normally retained by polySia molecules. Introduction of a single oxygen atom change into polySia by exogenous feeding of the non-neural sialic acid Neu5Gc (N-glycolylneuraminic acid) caused resistance to Neu1-induced polySia turnover and also inhibited the associated release of brain-derived neurotrophic factor. These results indicate the importance of rapid turnover of the polySia glycocalyx by exovesicular sialidases in neurotrophin regulation.
在原代小鼠小胶质细胞和小鼠小胶质细胞系Ra2上，已证实存在酸性糖萼，即唾液酸Neu5Ac（N-乙酰神经氨酸）的聚合物多唾液酸（polySia/PSA）的表达。已知多唾液酸主要在神经细胞上调节细胞黏附、迁移和神经营养因子的定位。在炎症刺激后，Ra2细胞上的多唾液酸迅速消失。敲低和抑制剂研究结果表明，多唾液酸的快速表面清除是通过作为外囊泡成分分泌内源性唾液酸酶Neu1来实现的。Neu1介导的多唾液酸周转伴随着通常被多唾液酸分子保留的脑源性神经营养因子的释放。通过外源添加非神经唾液酸Neu5Gc（N-羟乙酰神经氨酸）使多唾液酸引入单个氧原子变化，导致对Neu1诱导的多唾液酸周转产生抗性，并抑制相关的脑源性神经营养因子释放。这些结果表明外囊泡唾液酸酶对多唾液酸糖萼进行快速周转在神经营养因子调节中的重要性。
