万方数据万方数据·140·董方,等.平分型G1cNAc糖基化修饰的生物学功能蛋白分选的负性调节信号n21。
3.3生殖发育调控人类精子缺乏MHCI类分子,使其易于被NK细胞溶解。
而MHcI阴性的肿瘤细胞通过在肿瘤细胞表面表达足量的平分型N一聚糖,而阻断NK细胞的溶解作用。
因此,精细胞也可能通过同样的机翩选避NK的细胞溶解作用。
利用超敏质谱仪对精细胞N一聚糖测序可以检测到3类N一聚糖:①高甘露糖塑;②二天线平分型;③以hisx和IJewis丫作为终端修饰的二天线、三天线、四天线型。
糖蛋白染色显示,携带呐穿列糖蛋白分布于顶体莉不是位于浆膜;丽功能缺陷的精子则表现为抗娜抗体分布异常(图2)。
推测惨饰聚糖可以抑制生殖道内计对精子糖蛋白的抗原特异性免疫反嘘。
嘲』III匕,人类精子哟主要聚糖与先天性及获得性免疫反瘟哟抑制有关。
这些结果支持哺乳类动物表邀碳水化合物与|配子《耨删魄哆保护及人类在子宫棚哟发育有关。
某些特殊类型的细胞表达特异性糖姐模式,惜此发挥相嘘睡句生物学功能‘引。
嘲2久类储子表达的主要N-聚糖k:高甘露糖型(Ma呜9tol湖舢:);瞻::件有或不件宥核心者澡糖者藻糖修饰哟平分型二天线结构;lO:盖、兰、嘲毙线聚糖,板心砻澡糖岩藻糖修饰,镌带呱嫡毋致/或蜥r谬饰赃娠lf目关糖蜚囟【(畔e粤l堋呀啪舯幽峨硼挈蜘o_删坩i拣,‰9是反刍勘物滋养层细胞分泌韵主要蛋白。
,遨些蛋白储存在滋养屡巨大细胞分秘颗粒恂.,与母体子宫止发细胞融合后释放进入母体器。
雷。
妊娠串期Ip黻最丰寓的弘聚糖是四无线核心绪!藻糖基眈修饰辅构’,并连接有平分型蛾Nk。
组成湖8航塬[№№娆.,3(·G姗№鲫、49l创必.,删l渊№]哟聚糖均为删天线型。
采用识别铷薯睨原的单克糟醐谢:(心埴ll9对分泌颗粒染色,分断:显示、,鳃娠.娩出话歪分娩前数天.,可以检测判黜a航原的存在。
I山褴凝集素t(t脚溅i珏删脚I卜sislectin)(该凝集素可以与a2,3·唾液酸修饰的乳糖氨)组织化学分析显示,该分泌颗粒在妊娠32d及分娩前呈阳性。
提示在妊娠不同阶段PAGs的N一聚糖修饰模式有相应的改变,这些聚糖的不同糖型可能介导不同妊娠阶段的不同生理功能【l引。
平分型N一聚糖在发育调控中的具体功能虽然还不明确,但在进化上高度保守。
对斑马鱼的胚胎发育过程中N一聚糖表达动态分析显示,受精后4~7hN.聚糖仅仅可以检测到,但12—15hN一聚糖表达显著增加。
对这些聚糖的结构分析表明,含有或不含有岩藻糖和(或)平分型GlcNAc残基的复合型二天线N一聚糖是主要的表达聚糖¨5I。
3.4神经发育及再生与三甘露糖核心上Bl,4甘露糖相连接平分型GkNAc残基修饰的双天线N.聚糖在脑组织内含量丰富,被认为是脑型糖链。
脑组织来源的神经细胞系CG4半乳糖基转移酶I表达活性增强,即导致该脑型糖链合成的减少;该型糖链表达水平的高低决定于半乳糖基转移酶I活性的强弱。
半乳糖基转移酶活性表达增强也导致CG4细胞生长停滞及表型异常,并伴有细胞死亡率的增加,即便是半乳糖基转移酶I活性中等程度的增加,也会导致N.聚糖合成途径的中断,对CG4细胞是致死性的结局.1引。
提示中枢神经系统N.聚糖的平分型GlcNAc修饰在神经系统发育过程中具有重要调节作用。
在血清饥饿反应条件下,Neum2a细胞转染GnT.Ⅲ后可以诱导轴突样反应,整合素B1分布部位伴有神经突和突起形成。
这种神经纤维生成增强效应可被添加包含平分型GlcNAc的N.聚糖或植物血凝素(印曲I岫路l瓶na£iIlgph)rtohemaggluhin,E4一PHA)所抑钶,该凝集素主要识别平分型GlcNAc【4]。
Gnr.一的促神经纤维生成作用也可以被抗Bl整合素功能阻断抗体显著抑制。
事实上,pl整合素也是GnT一■的靶蛋白之一,也已经通过E4.PHA的础—曲帆船s啊分析所证实。
提示携带平分型Glc—NAc的N·聚糖对神经纤维再生具有一定调节作罔㈣。
大鼠嗜铬细胞瘤细胞系转染GIlT.Ⅲ,可抑制瞰F及整合素刺激神经突的生长。
这种神经突生长抑制作用可被丝裂原或细胞外信号调节激酶激酶.噩(趣缈小艘删蚰砌-【i嘲seki岫se_l,MEK.1>所逆转。
与此一致韵是,EGFR介导的ERK激活也可被舶BⅡ转染所阻滞;GnT一■突变(D32lA)则难以抑制神经突起韵生长;凝集素印迹分析显示,野生型GmB■转染细胞的EGnt的N一聚糖结万方数据万方数据万方数据万方数据平分型GlcNAc糖基化修饰的生物学功能作者:董芳, 肖凡, 魏红山, DONG Fang, XIAO Fan, WEI Hongshan作者单位:北京地坛医院,首都医科大学传染病研究所,北京市,100015刊名:医学分子生物学杂志英文刊名:JOURNAL OF MEDICAL MOLECULAR BIOLOGY年,卷(期):2009,6(2)被引用次数:0次1.ZHAO Y.SATO Y.ISAJI T Branched N-glycans regulate the biological functions of integrins and cadherins 2008(09)2.KARIYA Y.KATO R.ITOH S N-glycosylation of laminin-332 regulates its biological functions:A novel function of the bisecting GlcNAc 2008(48)3.FREY A D.KARG S R.KALLIO P T Expression of rat beta(1,4)-N-acetylglucosaminyltransferase Ⅲ in Nicotiana tabacum remodels the plant-specific N-glycosylation 2008(01)4.FERRARA C.BRüNKER P.SUTER T Modulation of therapeutic antibody effector functions by glycosylation engineering:influence of Golgi enzyme localization domain and co-expression of heterologous beta1,4-N-acetylglucosaminyltransferase Ⅲ and Golgi alpha-mannosidase Ⅱ 2006(05)5.ANDR S.KOZR 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Beta1,4-N-Acetylglucosaminyltransferase III down-regulates neurite outgrowth induced by costimulation of epidermal growth factor and integrins through the Ras/ERK signaling pathway in PC12 cells 2004(02)19.STANLEY P Biological consequences of overexpressing or eliminating N-acetylglucos-aminyltransferase-TIII in the mouse 2002(03)20.ISAJI T.GU J.NISHIUCHI R Introduction of bisecting GlcNAc into integrin alpha5beta1 reduces ligand binding and down-regulates cell adhesion and cell migration 2004(19)21.ZHAO Y.NAKAGAWA T.ITOH S N-acetylglucosaminyltransferase III antagonizes the effect of N-acetylglucosaminyl-transferase V on alpha3beta1 integrin-mediated cell migration 2006(43)22.YOSHIMURA M.IHARA Y.OHNISHI A Bisecting Nace-tylglucosamine on K562 cells suppresses naturalkiller cytotoxicity and promotes spleen colonization 1996(02)23.WUHRER M.STAM J C.VAN DE GEIJN F E Glycosylation profiling of immunoglobulin G(IgG)subclasses from human serum 2007(22)24.TAKEGAWA Y.DEGUCHI K.NAKAGAWA H Structural analysis of an N-glycan with "beta1-4 bisecting branch" from human serum IgG by negative-ion MSn spectral matching and exoglycosidase digestion 2005(18)25.MORELLE W.FLAHAUT C.MICHALSKI J C Mass spectrometric approach for screening modifications oftotal serum N-glycome in human diseases:application to cirrhosis 2006(04)26.MIYOSHI E.NISHIKAWA A.IHARA Y Selective suppression of N-acetylglucosaminyltransferase IIIactivity in a human hepatoblastoma cell line transfected with hepatitis B virus 1994(07)27.SHIM J K.LEE Y C.CHUNG T H Elevated expression of bisecting N-acetylglucosaminyl transferase-III gene in a human fetal hepatocyte cell line by hepatitis B virus 2004(12)28.AKASAKA-MANYA K.MANYA H.SAKURAI Y Increased bisecting and core-fucosylated N-glycans on mutant human amyloid precursor proteins 2008(08)29.ITOH N.SAKAUE S.NAKAGAWA H Analysis of N-glycan in serum glycoproteins from db/db mice and humans with type 2 diabetes 2007(04)30.BARBIN K.STIEGLMAIER J.SAUL D Influence of 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