N-glycan branching requirement in neuronal and postnatal viability.
N-glycan branching requirement in neuronal and postnatal viability.
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神经元和出生后活力中的 N-聚糖分支要求。
DOI：
10.1093/glycob/cwh069
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发表时间：
2004
期刊：
影响因子：
4.3
通讯作者：
Marth,JameyD
中科院分区：
文献类型：
--
作者：
Ye,Zhengyi;Marth,JameyD
细胞外n -聚糖的结构变化反映了在高尔基体中运作的糖基转移酶和糖苷酶的活性。与其他类型的脊椎动物聚糖相比，n -聚糖是高度分枝的低聚糖，具有多个触角连接到潜在的甘露糖核心结构。n -聚糖的分支模式包括三种类型，称为高甘露糖，杂化和复杂。虽然大多数细胞外哺乳动物n -聚糖是复杂的类型，一些细胞可变地表达杂交和高甘露糖形式。然而，在遗传有缺陷的emgat1或mgat2等位基因的小鼠和人类中，在胚胎发育和出生后功能中存在杂交和复杂n -聚糖分支的需求。形成n -聚糖分支模式的缺陷导致多种异常，包括神经缺陷，并推断在不同细胞系中存在不同功能的杂交和复杂n -聚糖分支。我们进一步探索了n -聚糖在体内的结构-功能关系，通过使用Cre-loxP条件诱变来消除神经元细胞中特异性的杂交和复杂n -聚糖分支。我们的研究结果表明，杂交n -聚糖分支是神经元翻译后必不可少的修饰。mgat1的缺失导致一种独特的神经元糖蛋白缺乏模式，同时伴有caspase 3的激活和凋亡。这些动物表现出严重的运动缺陷、震颤、麻痹和早期产后死亡。出乎意料的是，在没有神经元或运动功能障碍的表型标记的情况下，neuronalmgat2缺失导致复杂而非杂交n -聚糖分支的丢失是耐受良好的。与杂化n -聚糖分支相关的结构特征包括对神经元糖蛋白的必要翻译后修饰，从而允许正常的细胞功能和活力。
The structural variations among extracellular N-glycans reflect the activity of glycosyltransferases and glycosidases that operate in the Golgi apparatus. More than other types of vertebrate glycans, N-glycans are highly branched oligosaccharides with multiple antennae linked to an underlying mannose core structure. The branching patterns of N-glycans consist of three types, termed high-mannose, hybrid, and complex. Though most extracellular mammalian N-glycans are of the complex type, some cells variably express hybrid and high-mannose forms. Nevertheless, a requirement for hybrid and complex N-glycan branching exists in embryonic development and postnatal function among mice and humans inheriting defectiveMgat1orMgat2alleles. The resulting defects in formation N-glycan branching patterns cause multiple abnormalities, including neurologic defects, and have inferred the presence of distinct functions for hybrid and complex N-glycan branches among different cell lineages. We have further explored N-glycan structure-function relationshipsin vivoby using Cre-loxP conditional mutagenesis to abolish hybrid and complex N-glycan branching specifically among neuronal cells. Our findings show that hybrid N-glycan branching is an essential posttranslational modification among neurons. Loss ofMgat1resulted in a unique pattern of neuronal glycoprotein deficiency concurrent with caspase 3 activation and apoptosis. Such animals exhibited severe locomotor deficits, tremors, paralysis, and early postnatal death. Unexpectedly, neuronalMgat2deletion resulting in the loss of complex but not hybrid N-glycan branching was well tolerated without phenotypic markers of neuronal or locomotor dysfunction. Structural features associated with hybrid N-glycan branching comprise a requisite posttranslational modification to neuronal glycoproteins that permits normal cellular function and viability.
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影响因子：
4.3
作者：
CAMPBELL, RM;METZLER, M;MARTH, JD
通讯作者：
MARTH, JD
影响因子：
5.2
作者：
JAEKEN, J;SCHACHTER, H;SPIK, G
通讯作者：
SPIK, G
DOI：
10.1016/s0021-9258(18)45643-8
发表时间：
1987-04
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
B. Bendiak;H. Schachter
通讯作者：
B. Bendiak;H. Schachter
DOI：
10.1073/pnas.91.2.728
发表时间：
1994-01-18
影响因子：
11.1
作者：
IOFFE, E;STANLEY, P
通讯作者：
STANLEY, P
影响因子：
10.5
作者：
Zhu, Y;Romero, MI;Parada, LF
通讯作者：
Parada, LF