胺合成酶6的糖化是其活性所需的
Alexandra J Straus1, Grace Mavodza2, Can E Senkal3
1Department of Biochemistry and Molecular Biology, Virginia Commonwealth University School of Medicine, Richmond, VA, USA; C. Kenneth and Dianne Wright Center for Clinical and Translational Research, Virginia Commonwealth University School of Medicine, Richmond, VA, USA.
Journal of lipid research
|November 28, 2024
概括
在Asn18中糖化胺合成酶6 (CerS6) 对于其活性和下游信号提供至关重要. 这种翻译后修改调节了胺生成,但没有影响ER应力通路.
科学领域:
- 生物化学 生物化学
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
背景情况:
- 包括胺在内的脂对细胞膜结构和信号传递至关重要.
- 胺合成酶 (CerS) 酶产生胺,涉及到细胞应激和亡.
- 连接胺与内细胞网膜 (ER) 应激信号的确切机制尚不清楚.
研究的目的:
- 研究胺合成酶6 (CerS6) 糖化在调节其活性和细胞信号传递中的作用.
- 阐明布雷菲尔丁A (BFA) 对CerS6糖化和胺积累的影响.
- 为了确定CerS6糖化是否影响ER应激反应途径.
主要方法:
- 使用了HCT116CRISPR-Cas9CerS6淘汰细胞. 使用了HCT116CRISPR-Cas9CerS6淘汰细胞.
- 重新引入的野生型 (WT) CerS6或缺乏糖化酶的N18A突变CerS6.
- 在体外和现场评估CerS6活性.
- 分析了下游的信号通路,包括GSK3β,AKT,JNK和STAT3.
主要成果:
- 布雷菲尔丁A (BFA) 治疗增加了CerS6糖化和内源胺水平.
- 在Asn18发现CerS6的基底糖化对其酶活性至关重要.
- 与WT CerS6细胞相比,表达N18A突变CerS6的细胞的活性显著降低.
- N18A突变导致GSK3β,AKT,JNK和STAT3信号通路的缺陷.
- 没有发现Asn18糖化对ER应激反应途径产生影响.
结论:
- 翻译后修饰,特别是在Asn18的糖化,是CerS6活动的关键调节者.
- 对于高效的胺生成,CerS6糖化非常重要.
- 不调节CerS6糖化对多个下游细胞信号通路产生影响,独立于ER应激调制.
相关概念视频
Oligosaccharide Assembly
2.8K
Protein glycosylation starts in the ER lumen and continues in the Golgi apparatus. Glycosyltransferases catalyze the addition of sugar molecules or glycosylation of proteins. Usually, these enzymes add sugars to the hydroxyl groups of selected serine or threonine residues to form O-linked glycans or the amino groups of asparagine residues to form N-linked glycans. Different positions on the same polypeptide chain can contain differently linked glycans.
Multiple sugar molecules that may or may...
Multiple sugar molecules that may or may...
2.8K
Protein Glycosylation
6.8K
Glycosylation, the most common post-translational modification for proteins, serves diverse functions. Adding sugars to proteins makes the proteins more resistant to proteolytic digestion. Glycosylated proteins can act as markers and receptors to promote cell-cell adhesion. Additionally, they have many essential quality control functions in the cell, such as correct protein folding and facilitating transport of misfolded proteins to the cytosol, which can be degraded.
Glycosylation occurs in...
Glycosylation occurs in...
6.8K
Protein Folding Quality Check in the RER
3.7K
ER is the primary site for the maturation and folding of soluble and transmembrane secretory proteins. The calnexin cycle is a specific chaperone system that folds and assesses the confirmation of N-glycosylated proteins before they can exit the ER lumen. The primary players of this quality check pipeline are the lectins, ER-resident chaperones, and a glucosyl transferase enzyme. In case the calnexin system in the lumen fails to salvage a misfolded protein, it is transported to the cytoplasm...
3.7K
Biosynthesis of Polysaccharides
1
Polysaccharides such as glycogen and starch are synthesized from nucleoside diphosphate sugars, primarily uridine diphosphate glucose (UDPG) and adenosine diphosphate glucose (ADPG). These activated glucose donors act as key intermediates in carbohydrate metabolism and biosynthesis. UDPG primarily involves glycogen synthesis in animals and many bacteria, while ADPG plays a fundamental role in starch synthesis in plants and certain bacteria.UDPG is formed when glucose-1-phosphate reacts with...
1
Protein Modifications in the RER
5.0K
Modification of secretory and transmembrane proteins entering the rough ER begins in the ER lumen. These modifications aid in protein folding and stabilize the acquired tertiary structure. Protein modifications in the rough ER co-occur at different stages of protein folding.
Broadly, these modifications can be categorized into four main categories — glycosylation, formation of disulfide bonds, assembly of protein subunits, and specific proteolytic cleavages like removal of signal...
Broadly, these modifications can be categorized into four main categories — glycosylation, formation of disulfide bonds, assembly of protein subunits, and specific proteolytic cleavages like removal of signal...
5.0K
Peptidoglycan Synthesis
2
Structure of PeptidoglycanPeptidoglycan is a vital structural component of the bacterial cell wall, providing mechanical strength and shape to the cell. It consists of repeating units of two sugars—N-acetylglucosamine (NAG) and N-acetylmuramic acid (NAM)—linked by β-1,4 glycosidic bonds. These sugar chains are cross-linked by short peptide chains, forming a mesh-like polymer that surrounds the bacterial plasma membrane.Cytoplasmic Phase – Precursor SynthesisPeptidoglycan...
2


