PLCB3

更新于：2025-05-07

基本信息

别名

1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3、Phosphoinositide phospholipase C-beta-3、phospholipase C beta 3

+ [4]

简介

Catalyzes the production of the second messenger molecules diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3) (PubMed:20966218, PubMed:29122926, PubMed:37991948, PubMed:9188725). Key transducer of G protein-coupled receptor signaling: activated by G(q)/G(11) G alpha proteins downstream of G protein-coupled receptors activation (PubMed:20966218, PubMed:37991948). In neutrophils, participates in a phospholipase C-activating N-formyl peptide-activated GPCR (G protein-coupled receptor) signaling pathway by promoting RASGRP4 activation by DAG, to promote neutrophil functional responses (By similarity).

关联

100 项与 PLCB3 相关的临床结果

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100 项与 PLCB3 相关的转化医学

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0 项与 PLCB3 相关的专利（医药）

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160

项与 PLCB3 相关的文献（医药）

2025-01-01·Journal of Allergy and Clinical Immunology

Allergen-induced activation of epithelial P2Y2 receptors promotes adenosine triphosphate exocytosis and type 2 immunity in airways

Article

作者: Tojima, Ichiro ; Iijima, Koji ; O'Grady, Scott M ; Kita, Hirohito ; Srisomboon, Yotesawee

BACKGROUNDEnvironmental allergens induce the release of danger signals from the airway epithelium that trigger type 2 immune responses and promote airway inflammation.OBJECTIVEWe investigated the role of allergen-stimulated P2Y₂ receptor activation in regulating adenosine triphosphate (ATP), IL-33, and DNA release by human bronchial epithelial (hBE) cells and mouse airways.METHODSThe hBE cells were exposed to Alternaria alternata extract and secretion of ATP, IL-33, and DNA were studied in vitro. Molecular and cellular mechanisms were examined by biochemical and genetic approaches. Mice were treated intranasally with pharmacologic agents and exposed to Alternaria extract.RESULTSExposure of hBE cells to Alternaria extract stimulated P2Y₂ receptors coupled to phospholipase C β₃, leading to activation of multiple protein kinase C (PKC) isoforms and an increase in intracellular Ca²⁺ concentration. Small interfering RNAs targeting PKC δ or inhibiting PKC δ activity with delcasertib blocked exocytosis of ATP and reduced IL-33 and DNA secretion. Moreover, a peptide antagonist for myristoylated alanine-rich C-kinase substrate (MARCKS) reduced vesicular ATP release. A proximity ligand assay showed that Alternaria extract stimulated MARCKS desorption from the plasma membrane and delcasertib prevented the response. Finally, the P2Y₂ receptor antagonist AR-C118925XX and delcasertib blocked IL-33, DNA, and type 2 cytokine secretion in vivo in mice exposed to Alternaria.CONCLUSIONP2Y₂ receptor stimulation after allergen exposure promoted activation of PLC β₃, PKC δ, and MARCKS protein desorption from the apical membrane, which facilitated ATP exocytosis and subsequent secretion of IL-33 and DNA. Epithelial P2Y₂ receptors serve as primary sensors for aeroallergen-induced alarmin release by airway epithelial cells.

2024-10-01·Journal of Comparative Neurology

Cerebellar Molecular Signatures in Non‐Human Primates

Article

作者: Yamamoto, Tatsuya ; Higo, Noriyuki ; Ose, Takayuki ; Murata, Yumi ; Yoshida, Yuko ; Hayashi, Takuya

ABSTRACTCerebellar molecular signatures in primates remain largely unexplored. Here, we investigated the immunoreactivity of neuroplasticity‐related molecular markers, including aldolase C (Aldoc), phospholipase C beta 3 (PLCB3), and phospholipase C beta 4 (PLCB4) in the cerebellar cortex and associated nuclei of rhesus macaque monkeys (Macaca mulatta). Our main findings are as follows: First, the cerebellar vermis in macaques exhibited striped compartmentalization for all markers, with the striped expression boundary of PLCB3 being less distinct than those of Aldoc and PLCB4. Second, the striped pattern was less pronounced in the cerebellar hemisphere compared to the vermis, with signals in the hemisphere being predominantly intense throughout. Third, distinct zonal patterns and elevated signals for Aldoc and PLCB3 were observed in the cerebellar deep nuclei. Specifically, the fastigial nucleus displayed intense Aldoc signals in both caudal and rostral regions, while the dentate nucleus displayed strong Aldoc signals in both ventral and dorsal regions. Compared to previous rodent studies, the macaque cerebellum demonstrated a higher proportion of intense signal areas and distinct compartmentalization patterns in both cortical and deep nuclei. These findings offer crucial insights into the unique molecular organization of the primate cerebellum, enhancing our understanding of the advanced neuroplasticity, cognitive, and motor capabilities in primates.

2024-06-01·Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease

OSBPL2 compound heterozygous variants cause dyschromatosis, ichthyosis, deafness and atopic disease syndrome

Article

作者: Zhao, Jingjun ; Wang, Yumeng ; Yang, Yijun ; Zhou, Naihui ; Yang, Yifan ; Zhang, Si ; Pan, Chaolan ; Cao, Qiaoyu ; Zhang, Jingwen ; Wang, Xiaoxiao ; Li, Min ; Li, Ming ; Huang, Haisheng ; Zhou, Shengru ; Zhao, Anqi ; Yang, Jianqiu ; Chen, Fuying

PURPOSEIn this study, we identified and diagnosed a novel inherited condition called Dyschromatosis, Ichthyosis, Deafness, and Atopic Disease (DIDA) syndrome. We present a series of studies to clarify the pathogenic variants and specific mechanism.METHODSExome sequencing and Sanger sequencing was conducted in affected and unaffected family members. A variety of human and cell studies were performed to explore the pathogenic process of keratosis.RESULTSOur finding indicated that DIDA syndrome was caused by compound heterozygous variants in the oxysterol-binding protein-related protein 2 (OSBPL2) gene. Furthermore, our findings revealed a direct interaction between OSBPL2 and Phosphoinositide phospholipase C-beta-3 (PLCB3), a key player in hyperkeratosis. OSBPL2 effectively inhibits the ubiquitylation of PLCB3, thereby stabilizing PLCB3. Conversely, OSBPL2 variants lead to enhanced ubiquitination and subsequent degradation of PLCB3, leading to epidermal hyperkeratosis, characterized by aberrant proliferation and delayed terminal differentiation of keratinocytes.CONCLUSIONSOur study not only unveiled the association between OSBPL2 variants and the newly identified DIDA syndrome but also shed light on the underlying mechanism.

项与 PLCB3 相关的新闻（医药）

2023-02-06

·生物谷

STTT：突破！川大/首医大团队发现自闭症谱系障碍的新风险基因，抗炎药和催产素类似物是潜在干预方案

该研究发现了一个新的ASD风险基因SCGN，而且发现SCGN的缺失会破坏催产素信号，并异常激活炎症，最终导致导致类似自闭症的行为、损害大脑发育，而催产素和抗炎药物或可以减弱由SCGN缺失引起的ASD相每年的4月2日，是世界“自闭症儿童关爱日”，这是一群被称为“来自星星的孩子”：世界在他们面前，也不在他们面前，世界倒映在他们眼里，他们却什么都看不见，就像天上的星星，独居在自己的世界里。自闭症谱系障碍（ASD）是一组以交流和社会互动障碍为特征的异质神经发育疾病，包括自闭症、阿斯伯格综合征、不典型自闭症以及儿童瓦解性精神障碍。2021年，美国疾病控制与预防中心（CDC）发布的报告显示：每44名8岁儿童中就有一名（2.3%）被确认患有ASD[1]。 ASD患者主要表现为沟通和社会互动障碍，以及重复或受限的感觉运动行为。除了这些核心症状外，可能还会出现发育迟缓、智力障碍、焦虑、抑郁、胃肠道和免疫系统疾病等。鉴于ASD的临床特征异质性，一直没有针对这种疾病的有效治疗方法，现有的ASD治疗药物不仅效果不佳，而且还会产生巨大的副作用，因此进一步了解ASD的发病机制对于开发新的治疗策略是必不可少的。近日，由四川大学贾大、张小虎、莫显明，以及首都医科大学李巍共同领衔的研究团队，在Signal Transduction and Targeted Therapy在线发表了最新研究成果。在这项研究中，他们发现突触传递的调节因子促泌素（SCGN）是ASD的一个新的风险基因，SCGN缺失通过破坏激活大脑中的促炎反应和催产素信号导致自闭症行为，而用消炎药和催产素类似物治疗SCGN缺失的动物则可以纠正自闭症行为[2]。文章首页截图为了识别潜在的ASD风险基因，研究人员首先对ASD先证者（对ASD遗传性状进行家系调查时，其家系中第一个被确诊的那个人）及其父母进行了全外显子组测序，在参与研究的168例病例中，有2例确定存在SCGN突变（ASD0010和ASD0014）。这两名患者都表现出典型的ASD核心特征，包括通过CABS、ABC和CARS评分衡量的沟通和社交缺陷。此外，根据Gesell发育量表，这两名SCGN突变的ASD患者还表现出严重的发育迟缓。 SCGN的突变与ASD有关接下来研究人员使用CRISPR/Cas9基因编辑技术，生成了scgn基因缺失的斑马鱼模型，以确定scgn基因在社会行为和神经元发育中的作用。结果发现相比于scgn+/−、scgn−/−基因型的斑马鱼，scgn+/+基因型的斑马鱼的社交持续时间明显更长，表现出更强的社会凝聚力，也就是说scgn基因纯合或杂合缺失会导致斑马鱼的自闭症样行为。此外，研究人员还观察到scgn基因缺失损坏斑马鱼的大脑发育，与scgn+/+胚胎相比，scgn−/−胚胎的头部尺寸显著减小，反映斑马鱼大脑发育的的眼长和眼距也体现出类似的结果：与scgn+/+组相比，scgn−/−胚胎表现出明显更小的眼睛，眼睛之间的距离更短。 scgn缺失损害斑马鱼的神经元发育那么scgn缺失是如何导致ASD的呢？为了回答这个问题，研究人员使用RNA-seq比较了scgn+/+和scgn−/−的斑马鱼大脑和小鼠下丘脑的基因表达谱差异。基因集富集分析（GSEA）显示，两者的差异表达基因（DEGs）主要富集在神经递质受体活性等通路。有趣的是，在炎症和先天免疫反应信号等多种免疫调节通路中也有富集。为了进一步证实上述观察结果，研究人员进行定量RT-PCR比较了scgn缺失小鼠模型中免疫相关的多个基因的表达，结果发现scgn缺失导致促炎基因IL-6和TNF的上调。ELISA结果也表明，scgn−/−小鼠中IL-6和IL-1β蛋白水平升高。也就是说，scgn基因缺失会改变免疫反应，导致异常炎症。 scgn缺失会改变免疫反应由于scgn蛋白通常调节激素分泌，因此研究人员进一步比较了scgn+/+和scgn−/−小鼠的血清代谢组学差异。综合代谢组学和转录组分析的结果，研究人员发现，scgn缺失导致催产素信号和神经活性配体-受体相互作用通路中断，影响催产素通路中许多基因如Oxt、Ppp3cb和Plcb3的表达。此外，与年龄匹配的scgn+/+组相比，scgn+/−和scgn−/−斑马鱼大脑中的催产素mRNA和蛋白质水平均显著降低，scgn+/−和scgn−/−斑马鱼的血清催产素水平相对于scgn+/+对照组降低了31%。总之，这些数据表明，scgn的功能缺失导致斑马鱼和小鼠催产素减少。 scgn缺失影响催产素分泌那么抗炎药物的使用和催产素的补充是否可以挽救scgn缺失导致的异常炎症和神经元发育障碍呢？研究人员于是选择了两种抗炎药物地塞米松和阿司匹林，以及一种半衰期延长的催产素合成物卡贝催产素处理ASD动物模型。可以看到，0.5μM或1μM卡贝催产素处理1天后，scgn+/−和scgn−/−斑马鱼胚胎的IL-1β的表达明显减弱，其表达与未处理对照组相似，抗炎药地塞米松和阿司匹林处理也强烈降低了scgn+/−和scgn−/−斑马鱼中IL-1β的表达。此外，scgn缺失所导致的ASD表型也可以被上述三种药物改善，其中高剂量的卡贝催产素和阿司匹林表现出最显著的改善效果，1μM的卡贝催产素处理使近2/3的scgn−/−斑马鱼的社会互动恢复到正常对照的水平，而10μM阿司匹林处理则可以使1/3-1/2的斑马鱼的社会互动恢复到正常对照组水平。催产素类似物、抗炎药物可拮抗斑马鱼scgn缺失导致的ASD 总的来说，该研究发现了一个新的ASD风险基因SCGN，而且发现SCGN的缺失会破坏催产素信号，并异常激活炎症，最终导致导致类似自闭症的行为、损害大脑发育，而催产素和抗炎药物或可以减弱由SCGN缺失引起的ASD相关缺陷。上述研究提示，催产素和抗炎药物是SCGN缺乏患者的潜在治疗方法，在精准医疗时代，这些机制的阐明将有助于开发针对ASD的个性化治疗手段，拓宽目前有限的ASD治疗干预方法的选择。同时，这一研究成果也提示根据ASD患者的具体发病机制来提供不同的治疗手段是至关重要的，这可以极大地提高治疗的成功率。参考文献： [1] Jiang, Chen-Chen et al. “Signalling pathways in autism spectrum disorder: mechanisms and therapeutic implications.” Signal transduction and targeted therapy vol. 7,1 229. 11 Jul. 2022 [2] Liu, Zhe et al. “SCGN deficiency is a risk factor for autism spectrum disorder.” Signal transduction and targeted therapy vol. 8,1 3. 2 Jan. 2023