更新于：2024-09-19

CLSTN1

更新于：2024-09-19

基本信息

别名

Alc-alpha、Alcadein-alpha、Alzheimer-related cadherin-like protein

+ [12]

简介

Postsynaptic adhesion molecule that binds to presynaptic neurexins to mediate both excitatory and inhibitory synapse formation (By similarity). Promotes synapse development by acting as a cell adhesion molecule at the postsynaptic membrane, which associates with neurexin-alpha at the presynaptic membrane (By similarity). Also functions as a cargo in axonal anterograde transport by acting as a molecular adapter that promotes KLC1 association with vesicles (PubMed:21385839). Complex formation with APBA2 and APP, stabilizes APP metabolism and enhances APBA2-mediated suppression of beta-APP40 secretion, due to the retardation of intracellular APP maturation (PubMed:12972431). As intracellular fragment AlcICD, suppresses APBB1-dependent transactivation stimulated by APP C-terminal intracellular fragment (AICD), most probably by competing with AICD for APBB1-binding (PubMed:15037614). In complex with APBA2 and C99, a C-terminal APP fragment, abolishes C99 interaction with PSEN1 and thus APP C99 cleavage by gamma-secretase, most probably through stabilization of the direct interaction between APBA2 and APP (PubMed:15037614).

关联

100 项与 CLSTN1 相关的临床结果

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100 项与 CLSTN1 相关的转化医学

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0 项与 CLSTN1 相关的专利（医药）

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项与 CLSTN1 相关的文献（医药）

2024-07-05·Journal of Proteome Research

Identification of Candidate Protein Biomarkers Associated with Domoic Acid Toxicosis in Cerebrospinal Fluid of California Sea Lions (Zalophus californianus)

Article

作者: Bland, Alison M ; Whitmer, Emily R ; Janech, Michael G ; Field, Cara L ; Duignan, Pádraig J ; Neely, Benjamin A ; Ghosh, Gautam

Since 1998, California sea lion (Zalophus californianus) stranding events associated with domoic acid toxicosis (DAT) have consistently increased. Outside of direct measurement of domoic acid in bodily fluids at the time of stranding, there are no practical nonlethal clinical tests for the diagnosis of DAT that can be utilized in a rehabilitation facility. Proteomics analysis was conducted to discover candidate protein markers of DAT using cerebrospinal fluid from stranded California sea lions with acute DAT (n = 8), chronic DAT (n = 19), or without DAT (n = 13). A total of 2005 protein families were identified experiment-wide. A total of 83 proteins were significantly different in abundance across the three groups (adj. p < 0.05). MDH1, PLD3, ADAM22, YWHAG, VGF, and CLSTN1 could discriminate California sea lions with or without DAT (AuROC > 0.75). IGKV2D-28, PTRPF, KNG1, F2, and SNCB were able to discriminate acute DAT from chronic DAT (AuROC > 0.75). Proteins involved in alpha synuclein deposition were over-represented as classifiers of DAT, and many of these proteins have been implicated in a variety of neurodegenerative diseases. These proteins should be considered potential markers for DAT in California sea lions and should be prioritized for future validation studies as biomarkers.

2024-07-01·European Journal of Pain

Exploring biomarkers in trigeminal neuralgia patients operated with microvascular decompression: A comparison with multiple sclerosis patients and non‐neurological controls

Article

作者: Lafta, Muataz S ; Schiöth, Helgi B ; Sokolov, Aleksandr V ; Abu Hamdeh, Sami ; Ericson, Hans ; Landtblom, Anne-Marie

AbstractBackgroundTrigeminal neuralgia (TN) is a severe facial pain condition often associated with a neurovascular conflict. However, neuroinflammation has also been implicated in TN, as it frequently co‐occurs with multiple sclerosis (MS).MethodsWe analysed protein expression levels of TN patients compared to MS patients and controls. Proximity Extension Assay technology was used to analyse the levels of 92 proteins with the Multiplex Neuro‐Exploratory panel provided by SciLifeLab, Uppsala, Sweden. Serum and CSF samples were collected from TN patients before (n = 33 and n = 27, respectively) and after (n = 28 and n = 8, respectively) microvascular decompression surgery. Additionally, we included samples from MS patients (n = 20) and controls (n = 20) for comparison.ResultsIn both serum and CSF, several proteins were found increased in TN patients compared to either MS patients, controls, or both, including EIF4B, PTPN1, EREG, TBCB, PMVK, FKBP5, CD63, CRADD, BST2, CD302, CRIP2, CCL27, PPP3R1, WWP2, KLB, PLA2G10, TDGF1, SMOC1, RBKS, LTBP3, CLSTN1, NXPH1, SFRP1, HMOX2, and GGT5. The overall expression of the 92 proteins in postoperative TN samples seems to shift towards the levels of MS patients and controls in both serum and CSF, as compared to preoperative samples. Interestingly, there was no difference in protein levels between MS patients and controls.ConclusionsWe conclude that TN patients showed increased serum and CSF levels of specific proteins and that successful surgery normalizes these protein levels, highlighting its potential as an effective treatment. However, the similarity between MS and controls challenges the idea of shared pathophysiology with TN, suggesting distinct underlying mechanisms in these conditions.SignificanceThis study advances our understanding of trigeminal neuralgia (TN) and its association with multiple sclerosis (MS). By analysing 92 protein biomarkers, we identified distinctive molecular profiles in TN patients, shedding light on potential pathophysiological mechanisms. The observation that successful surgery normalizes many protein levels suggests a promising avenue for TN treatment. Furthermore, the contrasting protein patterns between TN and MS challenge prevailing assumptions of similarity between the two conditions and point to distinct pathophysiological mechanisms.

2024-04-01·Cardiovascular Drugs and Therapy

Calsyntenin-1 Promotes Doxorubicin-induced Dilated Cardiomyopathy in Rats

Article

作者: Cheng, Liting ; Guo, Ge ; Zhu, Mingxiang ; Shen, Yanying ; Chen, Yibing ; Li, Xin ; Li, Hanlu ; Liu, Chunlei ; Yang, Hao ; He, Kunlun ; Xu, Xiang

AbstractPurposeDoxorubicin is an important cancer chemotherapeutic agent with severe cardiotoxic effects that eventually lead to dilated cardiomyopathy (DCM). Calsyntenin-1(CLSTN1) plays a critical role in the nervous system, but its relevance in cardiovascular diseases is unknown. We investigated the significance of CLSTN1 in doxorubicin-induced DCM.MethodsCLSTN1 expression in doxorubicin-induced DCM rats and H9c2 cells was determined using western blotting. To further explore the functions of CLSTN1, a cardiac-specific CLSTN1 overexpression rat model was constructed. The rats were subjected to analysis using echocardiographic, hemodynamic, and electrocardiographic parameters. Potential downstream molecules in CLSTN1 overexpression heart tissue were investigated using proteomics and western blotting. Finally, a knockdown of CLSTN1 was constructed to investigate the rescue function on doxorubicin-induced cell toxicity.ResultsCLSTN1 protein expression increased drastically in doxorubicin-induced DCM rats and H9c2 cells. Under doxorubicin treatment, CLSTN1 protein-specific overexpression in the heart muscle promoted cardiac chamber enlargement and heart failure, while the knockdown of CLSTN1 reduced doxorubicin-induced cardiomyocyte toxicity in vitro. At the mechanistic level, overexpression of CLSTN1 downregulated SERCA2 expression and increased the phosphorylation levels of PI3K-Akt and CaMK2.ConclusionOur findings demonstrated that CLSTN1 promotes the pathogenesis of doxorubicin-induced DCM. CLSTN1 could be a therapeutic target to prevent the development of doxorubicin-induced DCM.

项与 CLSTN1 相关的新闻（医药）

2023-12-23

·今日头条

新发现！华中科技大学：发现胃癌转移新机制，揭示治疗新靶点

本文为转化医学网原创，转载请注明出处作者：Jerry 导读：肿瘤转移严重限制了胃癌患者的预后。RNA结合蛋白(RBPs)在肿瘤转移中起着至关重要的作用，但对其在胃癌中的作用的研究有限。 12月19日，华中科技大学刘炜圳/陶凯雄研究团队在期刊《Cell Death Discovery》上发表了题为“ESRP1-driven alternative splicing of CLSTN1 inhibits the metastasis of gastric cancer”的研究论文，该研究中，研究人员发现上皮细胞中RBP特异性的ESRP1在调节胃癌细胞的转移中起重要作用。ESRP1与胃癌患者远处转移和淋巴结转移呈负相关。研究人员在体外和体内证明了ESRP1抑制胃癌的迁移和侵袭。本研究突出了ESRP1在胃癌转移调控中的作用，并扩展了其机制。这些结果为ESRP1和CLSTN1成为胃癌转移的治疗靶点提供了可能。 https://www.nature.com/articles/s41420-023-01757-8 研究背景 01 胃癌是最常见的恶性肿瘤之一，每年超过100万例，占所有癌症诊断的5.6%。胃癌由于起病隐匿，缺乏具体的临床表现，常在晚期确诊，伴有局部、区域性或远处转移。肿瘤转移是影响胃癌预后的主要因素，早期胃癌5年生存率高达70%，晚期胃癌5年生存率不足30%。因此，筛选与胃癌转移相关的靶点，探讨其功能和潜在机制，有助于改善胃癌患者的治疗和预后。 RNA结合蛋白(RBPs)是一类进化上高度保守的蛋白质，具有RNA结合结构域，使其能够与RNA相互作用。RBPs占所有蛋白质编码基因的约10%。它们参与mRNA的选择性剪接调节、转运和定位，在维持基因组多样性和稳定性方面发挥重要作用。研究表明，RBPs与肿瘤发生发展密切相关，可通过调控pre- mrna选择性剪接影响肿瘤细胞增殖、上皮-间质转化(epithelial-mesenchymal transition, EMT)等过程。研究进展 02 为了进一步验证ESRP1对胃癌转移的影响，研究人员以内源性ESRP1表达水平较低的SGC7901和BGC823为基础，构建了2株ESRP1过表达胃癌细胞株。侵袭实验表明，过表达ESRP1后，胃癌细胞的迁移和侵袭能力下降。Ecadherin和Ncadherin是上皮-间质转化(epithelial-mesenchymal transition, EMT)的两个重要指标。研究人员还发现，胃癌细胞过表达ESRP1后，Ecadherin表达增加，Ncadherin表达减少，提示ESRP1可能抑制EMT过程。然后研究人员通过小鼠尾静脉注射实验验证了ESRP1在体内的功能。结果显示，esrp1过表达组肺转移瘤结节数量明显低于对照组。小鼠肺免疫组化结果显示，ESRP1过表达组肺转移灶中Ecadherin的表达显著升高。体外和体内研究表明，过表达ESRP1可抑制胃癌的迁移和侵袭 ESRP1敲低后，AGS细胞和MKN45细胞在侵袭实验中表现出迁移和侵袭增加，Ecadherin表达减少，Ncadherin表达增加，提示细胞可能发生间质转移，注射MKN45 shESRP1细胞小鼠肺转移结节增加，转移灶中Ecadherin蛋白水平降低进一步证实了这一点。这些结果表明，ESRP1抑制胃癌细胞的转移。为了研究CLSTN1在胃癌转移中的作用，研究人员构建了全长(CLSTN1- f)和截断(CLSTN1- s)过表达质粒。通过侵袭实验，研究人员发现过表达截断的CLSTN1 (CLSTN1- s)显著降低了胃癌细胞的迁移和侵袭，而过表达CLSTN1- f促进了胃癌细胞的迁移和侵袭。此外，研究人员检测了CLSTN1对关键EMT蛋白的影响，发现CLSTN1- s促进Ecadherin蛋白表达，抑制Ncadherin表达，而CLSTN1- f则相反，提示CLSTN1- s可能介导ESRP1诱导的胃癌转移抑制。这些结果表明CLSTN1-S在介导ESRP1抑制胃癌细胞转移中起关键作用。 CLSTN1外显子11剪接介导ESRP1诱导的胃癌细胞转移抑制研究结论 03 综上所述，本研究证实了ESRP1的表达和CLSTN1剪接水平在体外、体内和临床样品中与胃癌转移呈负相关。本研究为ESRP1-CLSTN1的分子调控及其在胃癌转移中的作用提供了新的见解。深入了解ESRP1-CLSTN1的分子调控将有助于设计治疗或预防胃癌转移的新策略。参考资料： https://www.nature.com/articles/s41420-023-01757-8 注：本文旨在介绍医学研究进展，不能作为治疗方案参考。如需获得健康指导，请至正规医院就诊。热门·直播/活动 🕓 北京｜12月19日-20日 ▶第四届单细胞测序技术应用研讨会暨单细胞&空间组学研讨会（日程稍后公布）点击对应文字查看详情

信使RNA