Journal of Biological Chemistry最新文献_第3页

Defined media reveals the essential role of lipid scavenging in supporting cancer cell proliferation. 定义介质揭示了脂质清除在支持癌细胞增殖中的重要作用。

IF 4 2区生物学

Journal of Biological Chemistry Pub Date : 2025-09-08 DOI: 10.1016/j.jbc.2025.110693

Oliver J Newsom, Eric Zheng, Lucas B Sullivan

{"title":"Defined media reveals the essential role of lipid scavenging in supporting cancer cell proliferation.","authors":"Oliver J Newsom, Eric Zheng, Lucas B Sullivan","doi":"10.1016/j.jbc.2025.110693","DOIUrl":"https://doi.org/10.1016/j.jbc.2025.110693","url":null,"abstract":"Fetal bovine serum (FBS) is an undefined additive that is ubiquitous to mammalian cell culture media and whose functional contributions to promoting cell proliferation remain poorly understood. Efforts to replace serum supplementation in culture media have been hindered by an incomplete understanding of the environmental requirements fulfilled by FBS. Here, we use a combination of live-cell imaging and quantitative lipidomics to elucidate the role of serum in supporting proliferation. We show that serum provides consumed factors that enable proliferation, with serum metal and lipid components serving as crucial metabolic resources. Despite access to a wide range of lipid classes available in serum, we find albumin-bound lipids are the primary species consumed by cancer cells. Furthermore, we find that supplementing with additives that contain necessary metals and any of the albumin-associated lipid classes can obviate the FBS requirement for cancer cell proliferation. Using this defined system, we investigated cancer cell lipid consumption dynamics, finding that albumin-associated lipids are primarily consumed through a mass-action mechanism with minimal competition within or amongst lipid classes. We also find that lipid scavenging is a dominant lipid acquisition route and is necessary for cancer cell proliferation. This work therefore identifies metabolic contributions of serum and provides a framework for building defined culture systems that sustain cell proliferation without the undefined contributions of serum.","PeriodicalId":15140,"journal":{"name":"Journal of Biological Chemistry","volume":" ","pages":"110693"},"PeriodicalIF":4.0,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145033239","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A diverse semi-synthetic humanized scFv phage display library for anti-CXCL16 antibodies. 抗cxcl16抗体的半合成人源化scFv噬菌体展示文库。

IF 4.8 2区生物学

Journal of Biological Chemistry Pub Date : 2025-09-08 DOI: 10.1016/j.jbc.2025.110692

ZhenSheng Li,Qi Chen,Shihui Wang,JianFeng Chen,ShiYang Chen

{"title":"A diverse semi-synthetic humanized scFv phage display library for anti-CXCL16 antibodies.","authors":"ZhenSheng Li,Qi Chen,Shihui Wang,JianFeng Chen,ShiYang Chen","doi":"10.1016/j.jbc.2025.110692","DOIUrl":"https://doi.org/10.1016/j.jbc.2025.110692","url":null,"abstract":"Phage display libraries of human single-chain variable fragments (scFv) serve as a valuable resource for generating fully human antibodies for scientific and clinical applications. In this study, we designed and constructed a highly diverse semi-synthetic humanized scFv phage display library using an optimized Kunkel mutagenesis approach. Our optimizations eliminated residual template, enhancing mutagenesis efficiency and expanding library diversity with a reservoir capacity exceeding 1010. For this semi-synthetic library, the complementarity-determining region 3 (CDR3) was structurally designed to mimic the natural human antibody repertoires, encompassing comprehensive sequence variability and length distributions. To functionally characterize this antibody library, we performed targeted screening against CXCL16, a crucial chemokine involved in inflammatory pathogenesis and tumor microenvironment regulation. We successfully identified multiple CXCL16 specific antibodies, one of which demonstrated strong blocking activity for the CXCL16-CXCR6 axis. Structural modeling and docking analyses further elucidated the key binding sites of CXCL16 and the antibody, offering insights for future antibody optimization. These results highlight the potential of this humanized scFv library as a robust platform for therapeutic antibody discovery, with broad applications in diagnostics and biomedical research.","PeriodicalId":15140,"journal":{"name":"Journal of Biological Chemistry","volume":"29 1","pages":"110692"},"PeriodicalIF":4.8,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145031921","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Nitric oxide regulates phagocytosis through S-nitrosylation of Rab5. 一氧化氮通过Rab5的s -亚硝基化调节吞噬作用。

IF 4 2区生物学

Journal of Biological Chemistry Pub Date : 2025-09-08 DOI: 10.1016/j.jbc.2025.110696

Makoto Hagiwara, Hiroyuki Tada, Kenji Matsushita

引用次数: 0

Tubulin hyperacetylation drives HMGB1 nuclear exit via the ROS-PARP1 axis leading to rotenone-induced G2/M Arrest. 微管蛋白超乙酰化通过ROS-PARP1轴驱动HMGB1核退出，导致鱼tenone诱导的G2/M阻滞。

IF 4 2区生物学

Journal of Biological Chemistry Pub Date : 2025-09-08 DOI: 10.1016/j.jbc.2025.110695

Sourav Dutta, Semanti Chakraborty, Ayushi Ghosh, Priyadarshini Halder, Shubhra Majumder, Ratnadip Paul, Somsubhra Nath, Piyali Mukherjee

{"title":"Tubulin hyperacetylation drives HMGB1 nuclear exit via the ROS-PARP1 axis leading to rotenone-induced G2/M Arrest.","authors":"Sourav Dutta, Semanti Chakraborty, Ayushi Ghosh, Priyadarshini Halder, Shubhra Majumder, Ratnadip Paul, Somsubhra Nath, Piyali Mukherjee","doi":"10.1016/j.jbc.2025.110695","DOIUrl":"https://doi.org/10.1016/j.jbc.2025.110695","url":null,"abstract":"Rotenone, a lipophilic pesticide, is strongly linked to dopaminergic neuronal loss primarily through mitochondrial complex I inhibition. Beyond its well-characterized neurotoxic effects, rotenone also triggers G2/M arrest in cells, but the molecular mechanisms linking this cell cycle perturbation to neurodegeneration remain unclear. Here, we identify HMGB1 as a key player in this process. HMGB1, known for its roles in genomic integrity and inflammation, exits the nucleus during rotenone-induced G2/M arrest, whereas its nuclear retention protects against mitotic DNA damage and subsequent cell cycle arrest. We found that rotenone-induced tubulin hyperacetylation precedes HMGB1 nuclear exit and is associated with increased mitochondrial ROS (mtROS) levels. Notably, reducing the levels of αTAT1 (alpha tubulin acetyltransferase 1) lowers mtROS production, preventing HMGB1 nuclear exit and subsequent rotenone-induced G2/M arrest. Although ROS is known to enhance tubulin acetylation, our findings reveal a bidirectional relationship in which tubulin acetylation regulates mtROS production and exacerbates cellular oxidative stress. Moreover, the PARP1 inhibitor PJ34 suppresses HMGB1 nuclear exit and rescues G2/M arrest, suggesting that mtROS-induced DNA damage elevates PARP1 activity, driving HMGB1 PARylation and subsequent translocation thus impairing DNA damage repair. Together, our findings uncover a previously unknown tubulin acetylation/mtROS/HMGB1 axis as a key driver of rotenone-induced G2/M arrest, highlighting the essential role of nuclear HMGB1 in maintaining genomic stability. Given that dopaminergic neurons in post-mortem PD brains exhibit G2/M arrest suggestive of abortive cell cycle re-entry, targeting this dysregulated axis may offer a promising strategy to mitigate rotenone-induced neurotoxicity.","PeriodicalId":15140,"journal":{"name":"Journal of Biological Chemistry","volume":" ","pages":"110695"},"PeriodicalIF":4.0,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145033252","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Biochemical characterization of a flavodiiron protein from bird parasite Histomonas meleagridis: superoxide as a reaction intermediate. 鸟寄生组织单胞菌黄二铁蛋白的生化特性：超氧化物作为反应中间体。

IF 4.8 2区生物学

Journal of Biological Chemistry Pub Date : 2025-09-04 DOI: 10.1016/j.jbc.2025.110685

Subrata Munan,Belem Yoval-Sánchez,Canglin Yao,Javier Seravalli,Evana N Abdulaziz,Mina L Heacock,Achyuta Ramesh,Alexander Galkin,Valentin Cracan

{"title":"Biochemical characterization of a flavodiiron protein from bird parasite Histomonas meleagridis: superoxide as a reaction intermediate.","authors":"Subrata Munan,Belem Yoval-Sánchez,Canglin Yao,Javier Seravalli,Evana N Abdulaziz,Mina L Heacock,Achyuta Ramesh,Alexander Galkin,Valentin Cracan","doi":"10.1016/j.jbc.2025.110685","DOIUrl":"https://doi.org/10.1016/j.jbc.2025.110685","url":null,"abstract":"Histomonas meleagridis is a parasitic protozoan which causes histomoniasis (blackhead disease) in a wide range of birds, including domesticated chickens and turkeys, representing a significant health problem in avian veterinary medicine. Despite being classified as an anaerobic parasite, H. meleagridis can survive transient exposure to oxygen while little is known about the mechanisms that allow this organism to cope with exposure to varying oxygen levels. Inspecting the H. meleagridis genome revealed that this organism possesses two flavodiiron proteins (FDPs) belonging to Classes A and F, which are known in other organisms to reduce O2 to H2O. The Class F FDP found in H. meleagridis (HmFDPF) has domain organization previously described for similar proteins and contains a middle rubredoxin-like and C-terminal NADH:rubredoxin oxidoreductase (NROR) domains in addition to an N-terminal FDP core. Here, we present extensive biochemical characterization of this protein to improve understanding of the coordinated activities of multiple redox centers that enable NADH-dependent reduction of O2 to H2O. We found that although superoxide is a HmFDPF reaction intermediate, only a very small amount of H2O2 is released as a byproduct. Moreover, HmFDPF does not possess NADH:H2O2 oxidoreductase activity and the enzyme is prone to quick inactivation by H2O2. In summary, our work expands our understanding of how microaerophilic protozoan parasites maintain their optimal redox state and minimize oxygen presence in their local environment, revealing mechanisms that can be exploited as drug targets against microaerophilic parasites.","PeriodicalId":15140,"journal":{"name":"Journal of Biological Chemistry","volume":"15 1","pages":"110685"},"PeriodicalIF":4.8,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145007106","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Dominant-negative NARS1 R534* mutation causes wild-type subunit poisoning and heterodimer predominance in cells. 显性阴性NARS1 R534*突变引起野生型亚基中毒和异源二聚体在细胞中的优势。

IF 4.8 2区生物学

Journal of Biological Chemistry Pub Date : 2025-09-04 DOI: 10.1016/j.jbc.2025.110690

Ingrid Vallee,Ryan Shapiro,Leo Qi,Marisa I Mendes,Desiree E C Smith,Qian Zhang,Taisuke Kanaji,Bernhard Kuhle,Xiang-Lei Yang

{"title":"Dominant-negative NARS1 R534* mutation causes wild-type subunit poisoning and heterodimer predominance in cells.","authors":"Ingrid Vallee,Ryan Shapiro,Leo Qi,Marisa I Mendes,Desiree E C Smith,Qian Zhang,Taisuke Kanaji,Bernhard Kuhle,Xiang-Lei Yang","doi":"10.1016/j.jbc.2025.110690","DOIUrl":"https://doi.org/10.1016/j.jbc.2025.110690","url":null,"abstract":"Aminoacyl-tRNA synthetases (aaRSs) catalyze the aminoacylation of tRNA with their cognate amino acids, an essential step in protein biosynthesis. While biallelic mutations in aaRSs often result in severe multi-organ dysfunction accompanied by developmental delays, monoallelic mutations typically cause milder, tissue-specific symptoms. However, a de novo monoallelic nonsense mutation (R534*) in the asparaginyl-tRNA synthetase (AsnRS)-resulting in a premature stop codon and 15-residue C-terminal truncation-has been identified in multiple families and is associated with severe neurodevelopmental symptoms. Here, we find that patient-derived lymphoblasts express similar amounts of wild-type (WT) and mutant (R534*) AsnRS and exhibit a severe proliferation defect. Like most aaRS family members, AsnRS functions as a homodimer. Structural analysis indicates that the region deleted in AsnRSR534* (R534-P548) contributes to dimerization, tRNA binding, and stabilization of the catalytic site architecture. Indeed, AsnRSR534*forms a weaker homodimer than AsnRSWT, displays impaired tRNA binding, along with a severe loss of enzymatic activity. Nevertheless, when exogenously expressed in human cells, AsnRSR534* shows a much stronger tendency than AsnRSWT to dimerize with the endogenous WT enzyme, driving R534*/WT heterodimer predominance in the cell. Notably, the heterodimer is severely defective in enzymatic function, comparable to the AsnRSR534*homodimer, indicating that AsnRSR534*exerts a dominant-negative loss-of-function effect on the WT subunit through heterodimerization. These findings provide a mechanistic explanation for how a monoallelic AsnRS mutation can lead to profound cellular dysfunction and contribute to severe neurodevelopmental disease, offering new insights into aaRS-associated pathologies and potential therapeutic strategies.","PeriodicalId":15140,"journal":{"name":"Journal of Biological Chemistry","volume":"103 1","pages":"110690"},"PeriodicalIF":4.8,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145007110","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The bacterial tRNA modifying enzyme tRNAIle2 lysidine synthetase is genetically conserved but catalytically variable. 细菌tRNA修饰酶tRNAIle2赖苷合成酶是遗传保守的，但催化变化。

IF 4.8 2区生物学

Journal of Biological Chemistry Pub Date : 2025-09-04 DOI: 10.1016/j.jbc.2025.110688

Marc J Muraski,Ferdiemar C Guinto,Emil M Nilsson,Jorge B Dabdoub,Samantha C Robinson,Yiyang Jiang,Zhen Shen,Rebecca W Alexander

引用次数: 0

Biochemical reconstitution of temozolomide-induced mutational processes. 替莫唑胺诱导突变过程的生化重建。

IF 4.8 2区生物学

Journal of Biological Chemistry Pub Date : 2025-09-04 DOI: 10.1016/j.jbc.2025.110676

Mahima R Sanyal,Tomohiko Sugiyama

{"title":"Biochemical reconstitution of temozolomide-induced mutational processes.","authors":"Mahima R Sanyal,Tomohiko Sugiyama","doi":"10.1016/j.jbc.2025.110676","DOIUrl":"https://doi.org/10.1016/j.jbc.2025.110676","url":null,"abstract":"Temozolomide (TMZ), a DNA alkylator, is a chemotherapeutic agent for brain tumors, but the treatment induces a distinct pattern of mutations, known as a cancer mutational signature SBS11. Although the correlation between TMZ treatment and SBS11 mutations is very clear, the precise biochemical mechanisms that cause SBS11 have not been elucidated. TMZ can alkylate DNA at several locations, among which O6-methylguanine (O6me-G) is believed to be most toxic. In this study, we reconstituted potential biochemical processes of TMZ-induced mutagenesis in vitro, including TMZ-induced DNA damage and subsequent DNA synthesis by various DNA polymerases. Next generation sequencing of the DNA products revealed mutations with a similar spectrum to SBS11. Efficient production of the SBS11-like mutation spectra required DNA in double-stranded form and multiple exposures to TMZ. Replicative polymerase δ alone generated SBS11-like mutations on the damaged DNA. Most SBS11-like mutations were sensitive to methyl guanine methyltransferase (MGMT) treatment, indicating that the mutations are formed on O6me-G modifications. Human Pol η reduced the SBS11-like mutations, indicating its suppressive role in TMZ-induced mutagenesis. Yeast Pol ζ and human Pol κ generated distinct mutations unrelated to SBS11.","PeriodicalId":15140,"journal":{"name":"Journal of Biological Chemistry","volume":"13 1","pages":"110676"},"PeriodicalIF":4.8,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145007107","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The long noncoding RNA SNHG12 defines KEAP1 stability and ferroptosis susceptibility by targeting E3 ligase TRIM25. 长链非编码RNA SNHG12通过靶向E3连接酶TRIM25来定义KEAP1的稳定性和铁下垂易感性。

IF 4.8 2区生物学

Journal of Biological Chemistry Pub Date : 2025-09-04 DOI: 10.1016/j.jbc.2025.110689

Yubo Guo,Shuang Zhu,Wenjie Wu,Yifan Cai,Sheikh Arslan Sehgal,Fang Huang,Hao Wu

{"title":"The long noncoding RNA SNHG12 defines KEAP1 stability and ferroptosis susceptibility by targeting E3 ligase TRIM25.","authors":"Yubo Guo,Shuang Zhu,Wenjie Wu,Yifan Cai,Sheikh Arslan Sehgal,Fang Huang,Hao Wu","doi":"10.1016/j.jbc.2025.110689","DOIUrl":"https://doi.org/10.1016/j.jbc.2025.110689","url":null,"abstract":"Ferroptosis is a novel type of programmed cell death caused by iron-dependent lipid peroxidation. Targeted induction of ferroptosis holds great promise for cancer treatment. SNHG, a newly recognized lncRNA family, has been reported to implicate in the proliferation, invasion, migration or drug resistance of cancer cells. Herein, we reported a SNHG member, SNHG12, is a novel ferroptosis regulatory lncRNA. Our data indicate that SNHG12 is upregulated during ferroptosis induction, with P53 potentially functioning as its transcription factor. In our experimental models, SNHG12 silence suppresses, while ectopic expression of SNHG12 expedites, Erastin- and RSL3-induced ferroptosis. Mechanistically, SNHG12 interact with the ubiquitin E3 ligase TRIM25, competitively interferes the TRIM25-KEAP1 interaction. The interaction of SNHG12-TEIM25 appears to preserve KEAP1 from TRIM25-mediated ubiquitination and proteasomal degradation. Consequently, SNHG12 restrain the antioxidant response of NRF2 to elevate the intracellular labile iron pool and accelerate GSH exhaustion in response to pro-ferroptotic insults, thereby modulating ferroptosis susceptibility in cancer cells. Collectively, our findings propose a novel regulatory circuit modulating ferroptosis, comprising SNHG12-TRIM25-KEAP1, and highlight the potential application of manipulating this regulatory axis in cancer treatment through ferroptosis.","PeriodicalId":15140,"journal":{"name":"Journal of Biological Chemistry","volume":"40 1","pages":"110689"},"PeriodicalIF":4.8,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145007108","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

WNT7A/B assemble a GPR124-RECK-LRP5/6 co-receptor complex to activate β-catenin signaling in brain endothelial cells. WNT7A/B组装GPR124-RECK-LRP5/6共受体复合物激活脑内皮细胞β-catenin信号传导。

IF 4.8 2区生物学

Journal of Biological Chemistry Pub Date : 2025-09-04 DOI: 10.1016/j.jbc.2025.110682

Robin Heiden,Laura Hannig,Calvin J Kuo,Süleyman Ergün,Barbara M Braunger,Mario Vallon

{"title":"WNT7A/B assemble a GPR124-RECK-LRP5/6 co-receptor complex to activate β-catenin signaling in brain endothelial cells.","authors":"Robin Heiden,Laura Hannig,Calvin J Kuo,Süleyman Ergün,Barbara M Braunger,Mario Vallon","doi":"10.1016/j.jbc.2025.110682","DOIUrl":"https://doi.org/10.1016/j.jbc.2025.110682","url":null,"abstract":"WNT7A and WNT7B, secreted by neural cells, are essential regulators of developmental brain angiogenesis and blood-brain barrier integrity. In brain endothelial cells, WNT7 proteins activate β-catenin signaling through the ligand-specific receptor complex GPR124-RECK and classical WNT receptors of the FZD and LRP families. Previous studies suggested that WNT7 isoforms assemble a GPR124-RECK-FZD-LRP5/6 multi-receptor complex for signaling. However, direct biochemical evidence for this complex and its signaling mechanisms remains elusive. Here, we investigated the formation and signaling mechanisms of WNT7 co-receptor complexes in brain endothelial cells using CRISPR/Cas9, biochemical analyses, and cell-based assays. Unexpectedly, cells with knockout of all FZD isoforms retained ∼25% of WNT7 responsiveness, whereas classical WNT3A signaling was completely abolished. Similarly, knockout of all Dvl paralogs, key mediators of FZD signaling, preserved ∼50% of WNT7 signaling activity but fully blocked WNT3A responses. In contrast, knockout of Gpr124, Reck, or Lrp5/6 completely abrogated WNT7 signaling. While both WNT7A and WNT3A triggered LRP6 phosphorylation, only WNT3A induced DVL2 phosphorylation. Biochemical analyses revealed WNT7-dependent recruitment of LRP5/6, but not FZD, to the GPR124-RECK heterodimer, forming a GPR124-RECK-WNT7-LRP5/6 complex. In GPR124-deficient cells, WNT7 proteins still assembled a RECK-WNT7-LRP5/6 core complex, yet this complex lacked signaling activity and LRP6 phosphorylation. Clustering of RECK-WNT7-LRP5/6 complexes with recombinant dimeric GPR124 ectodomain or a RECK antibody partially restored signaling, suggesting that GPR124 mediates formation of higher-order complexes. Our findings indicate that WNT7 signaling in brain endothelial cells is driven by distinct co-receptor complexes: a FZD-independent GPR124-RECK-LRP5/6 complex and FZD-dependent complexes that likely act in synergy.","PeriodicalId":15140,"journal":{"name":"Journal of Biological Chemistry","volume":"3 1","pages":"110682"},"PeriodicalIF":4.8,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145007109","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0