更新于：2024-09-19

WNT8B

更新于：2024-09-19

基本信息

别名

Protein Wnt-8b、Wnt family member 8B、WNT8B

简介

Ligand for members of the frizzled family of seven transmembrane receptors. May play an important role in the development and differentiation of certain forebrain structures, notably the hippocampus.

关联

100 项与 WNT8B 相关的临床结果

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100 项与 WNT8B 相关的转化医学

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0 项与 WNT8B 相关的专利（医药）

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108

项与 WNT8B 相关的文献（医药）

2024-07-01·Journal of Orthopaedic Translation

Wnt/β-catenin signaling pathway as an important mediator in muscle and bone crosstalk: A systematic review

Review

作者: Cheung, Wing Hoi ; Chai, Senlin ; Liu, Chaoran ; Chow, Simon Kwoon Ho ; Zhang, Ning ; Wong, Ronald Man Yeung ; Wang, Qianjin ; Lin, Wujian ; Cui, Can

BackgroundThe interaction between muscle and bone is shown to be clinically important but the underlying mechanisms are largely unknown. The canonical Wnt/β-catenin signaling pathway is reported to be involved in muscle-bone crosstalk, but its detailed function remains unclear. This systematic review aims to investigate and elucidate the role of the Wnt/β-catenin signaling pathways in muscle-bone crosstalk.MethodsWe conducted a literature search on the Web of Science, PubMed, EBSCO and Embase with keywords "Wnt*", "bone*" and "muscle*". A systematic review was completed according to the guideline of preferred reporting items of systematic reviews and meta-analyses (PRISMA). Data synthesis included species (human, animal or cell type used), treatments involved, outcome measures and key findings with respect to Wnts.ResultsSeventeen papers were published from 2007 to 2021 and were extracted from a total of 1529 search results in the databases of Web of Science (468 papers), PubMed (457 papers), EBSCO (371) and Embase (233). 12 Wnt family members were investigated in the papers, including Wnt1, Wnt2, Wnt2b, Wnt3a, Wnt4, Wnt5a, Wnt8a, Wnt8b, Wnt9a, Wnt10a, Wnt10b and Wnt16. Many studies showed that muscles were able to increase or decrease osteogenesis of bone, while bone increased myogenesis of muscle through Wnt/β-catenin signaling pathways. Wnt3a, Wnt4 and Wnt10b were shown to play important roles in the crosstalk between muscle and bone.ConclusionsWnt3a, Wnt4 and Wnt10b are found to play important mediatory roles in muscle-bone crosstalk. The role of Wnt4 was mostly found to regulate muscle from the bone side. Whilst the role of Wnt10b during muscle ageing was proposed, current evidence is insufficient to clarify the specific role of Wnt/β-catenin signaling in the interplay between sarcopenia and osteoporosis. More future studies are required to investigate the exact regulatory roles of Wnts in muscle-bone crosstalk in musculoskeletal disease models such as sarcopenia and osteoporosis.Translational potential of this articleThe systematic review provides an extensive overview to reveal the roles of Wnt/β-catenin signaling pathways in muscle-bone crosstalk. These results provide novel research directions to further understand the underlying mechanism of sarcopenia, osteoporosis, and their crosstalk, finally helping the future development of new therapeutic interventions.

2024-07-01·iScience

Zebrafish models of candidate human epilepsy-associated genes provide evidence of hyperexcitability

Article

作者: Robens, Barbara ; Ullmann, Jeremy F P ; McGraw, Christopher M ; Rotenberg, Alexander ; Turner, Laura ; Koh, Hyun Yong ; Poduri, Annapurna H ; Shao, Wanqing ; LaCoursiere, Christopher Mark ; Baker, Cristina M

Hundreds of novel candidate human epilepsy-associated genes have been identified thanks to advancements in next-generation sequencing and large genome-wide association studies, but establishing genetic etiology requires functional validation. We generated a list of >2,200 candidate epilepsy-associated genes, of which 48 were developed into stable loss-of-function (LOF) zebrafish models. Of those 48, evidence of seizure-like behavior was present in 5 (arfgef1, kcnd2, kcnv1, ubr5, and wnt8b). Further characterization provided evidence for epileptiform activity via electrophysiology in kcnd2 and wnt8b mutants. Additionally, arfgef1 and wnt8b mutants showed a decrease in the number of inhibitory interneurons in the optic tectum of larval animals. Further, RNA sequencing (RNA-seq) revealed convergent transcriptional abnormalities between mutant lines, consistent with their developmental defects and hyperexcitable phenotypes. These zebrafish models provide strongest experimental evidence supporting the role of ARFGEF1, KCND2, and WNT8B in human epilepsy and further demonstrate the utility of this model system for evaluating candidate human epilepsy genes.

2024-04-01·Cellular Signalling

HMGB1-mediated transcriptional activation of circadian gene TIMELESS contributes to endometrial cancer progression through Wnt-β-catenin pathway

Article

作者: Xin, Liqing ; Wang, Zhaoxia ; Wang, Fuyuan ; Zhao, Le ; Zhou, Ying ; He, Simin

TIMELESS (TIM) is a circadian gene which is implicated in the regulation of daily rhythm, DNA replication and repair, and cancer initiation and progression. Nevertheless, the role of TIM in endometrial cancer (EC) development is largely unknown. Bioinformatics analysis showed that TIM was aberrantly up-regulated in EC tissues and positively correlated with clinical or histological grade of EC. Functional studies showed that TIM knockdown reduced EC cell viability and restrained EC cell migration in vitro, as well as blocked xenograft tumor growth in vivo. Mechanistically, HMGB1 transcriptionally up-regulated TIM expression in EC cells. In addition, TIM could activate the transcription of the canonical Wnt ligand WNT8B, and TIM depletion could reduce the malignant potential of EC cells largely by targeting and down-regulating WNT8B. As a conclusion, HMGB1/TIM/WNT8B signal cascade was identified in this study for the first time. HMGB1 exerted its oncogenic role by activating the transcription of TIM, leading to the activation of Wnt signaling and EC progression.

项与 WNT8B 相关的新闻（医药）

2023-10-20

·生物谷

Cell：李晓淳团队揭示Wnt生物发生和分泌以及Wnt7特异性信号的分子基础

该研究以Wnt7a的合成、分泌和激活入手，阐释了脂修饰的Wnt蛋白是如何在ER中完成由PORCN向WLS的转移，WLS如何在细胞表面释放Wnt，以及中枢神经中Wnt7 特异性共受体RECK是如何发挥功德克萨斯大学西南医学中心李晓淳实验室在 Cell 期刊发表了题为：Molecular basis of Wnt biogenesis, secretion and Wnt7 specific signaling 的研究论文【2】。该研究以Wnt7a的合成、分泌和激活入手，阐释了脂修饰的Wnt蛋白是如何在ER中完成由PORCN向WLS的转移，WLS如何在细胞表面释放Wnt，以及中枢神经中Wnt7 特异性共受体RECK是如何发挥功能的。为了鉴定ER中参与Wnt蛋白合成的因子，研究团队在HEK293细胞中共表达了Wnt7a-WLS-RECK复合物。电镜结构显示出一个未知内源性蛋白结合Wnt7a，质谱鉴定和AlphaFold结构预测指出该蛋白为钙网蛋白（calreticulin，CALR）。CALR的Lectin 结构域主要作用于Wnt7a 的第295位天冬酰胺糖基化修饰，此修饰位点在大部分Wnt中保守。当在Wnt7a或Wnt3a中突变掉该糖基化位点时，突变体丧失了与CALR的结合能力，同时分泌量减少，激活下游信号能力显著减弱。为了探究Wnt蛋白在被PORCN脂化时是否有CALR参与，研究团队共表达了PORCN和Wnt蛋白，CoIP实验显示，在Wnt蛋白存在的情况下，过表达的PORCN，内源WLS，内源CALR能够和Wnt蛋白形成四元复合物，加上对结构的分析，研究团队得出CALR通过稳定Wnt蛋白来帮助其从PORCN到WLS转运的结论。研究团队对其他18种Wnt蛋白进行氨基酸序列比对和CoIP实验，结果显示除了Wnt8a、Wnt8b、Wnt9a和Wnt9b，CALR参与其他15种Wnt的合成，揭示了CALR对于Wnt蛋白的折叠，转运和合成中具有重要作用。为了进一步探究Wnt蛋白是如何从WLS上释放的，研究团队又解析了单独的WLS结构。与Wnt7a-WLS复合物结构对比发现，复合物的WLS跨膜区间结合了一个磷脂分子，该结果与已经报道的Wnt8a-WLS结构（Cell 184:194）和Wnt3a-WLS结构（Nature Communications 12: 4541）类似。但是单独的WLS并没有结合磷脂分子，而且其跨膜区发生了显著的构像变化，使结合Wnt蛋白hairpin2和脂修饰的口袋闭合。另外，虽然磷脂分子没有直接参与和Wnt7a的互作，但是CoIP实验和分子动力学实验证明磷脂分子对于WLS结合Wnt7a非常重要，因此该研究首次提出由磷脂分子介导的Wnt从WLS释放模型。有趣的是，通过分析单独的WLS结构，他们发现WLS跨膜区存在一个空腔，可以作为其抑制剂的结合位点，抑制Wnt的分泌，为靶向WLS的药物设计提供了重要依据。此外，通过对Wnt7a-RECKCC4复合物结构的分析，作者发现作为Wnt7a的特异受体， RECK的CC4结构域结合在Wnt7a的N端结构域。参与RECK互作的氨基酸在其他17种Wnt蛋白里面是不保守的，突变二者相互作用的氨基酸会减弱Wnt7a介导的信号活性，从而揭示了RECK实现对Wnt7特异性的机理。 Wnt合成分泌以及Wnt7a信号通路示意图总而言之，这项工作通过结构生物学，生物化学和细胞生物学的方法鉴定了第一个Wnt合成中的伴侣蛋白，提出了Wnt合成和分泌的新模型，并且阐释了Wnt7共受体的作用。该研究为抗癌药物研发，中枢神经中血脑屏障修复提供了分子模型。