Genes to Cells最新文献_第2页

RNF213-Dependent EGFR and HER2 Activation Regulates Specific Downstream Signaling Pathways in Human Cancer Cells 依赖rnf213的EGFR和HER2激活调节人类癌细胞特异性下游信号通路

IF 1.3 4区生物学

Genes to Cells Pub Date : 2025-06-12 DOI: 10.1111/gtc.70033

Intisar M. Fouad, Jungmi Choi, Qianying Huang, Minsoo Kim, Seiji Masuda, James A. Hejna, Yohei Mineharu, Akio Koizumi, Tohru Tezuka, Shohab Youssefian

{"title":"RNF213-Dependent EGFR and HER2 Activation Regulates Specific Downstream Signaling Pathways in Human Cancer Cells","authors":"Intisar M. Fouad, Jungmi Choi, Qianying Huang, Minsoo Kim, Seiji Masuda, James A. Hejna, Yohei Mineharu, Akio Koizumi, Tohru Tezuka, Shohab Youssefian","doi":"10.1111/gtc.70033","DOIUrl":"https://doi.org/10.1111/gtc.70033","url":null,"abstract":"In this study, we reveal a novel relationship between RNF213, an E3 ubiquitin ligase associated with Moyamoya disease (MMD) and the ubiquitination of both endogenous and pathogenic substrates, and EGFR, the epithelial growth factor receptor involved in cell growth, angiogenesis, and cancer. RNF213 knockdown or knockout in HeLa and A549 cells markedly reduces EGFR phosphorylation at key tyrosine sites following EGF and TGFα stimulation. In RNF213 knockout cells, HER2 phosphorylation, typically activated through heterodimerization with EGFR, and Src recruitment and/or phosphorylation are also diminished. Mutations in the RNF213 RING, RZ finger, or AAA+ domains, including the prevalent R4810K mutation in MMD, consistently reduce EGFR phosphorylation. In vivo, EGF injections increase EGFR and HER2 phosphorylation in WT but not in RNF213 knockout mice. Despite the reduced phosphorylation levels of these tyrosine kinases in knockout cells, the activation of downstream signals such as AKT, ERK1/2, and STAT3 remains unaffected, although phosphorylation of PLCγ, a key mediator of Ca2+ release, is selectively reduced by RNF213 knockout. These findings demonstrate that RNF213 modulates EGFR-related pathways and specific downstream signal pathways, possibly affecting physiologic and pathogenic angiogenesis, and may have implications for unraveling the etiology of MMD and for developing cancer therapies that target RNF213.","PeriodicalId":12742,"journal":{"name":"Genes to Cells","volume":"30 4","pages":""},"PeriodicalIF":1.3,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/gtc.70033","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144264371","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Microenvironment-Dependent MSC Immunoregulation in Type 1 Diabetes: Insights From IFNγ Preconditioning 1型糖尿病中依赖微环境的MSC免疫调节：来自IFNγ预处理的见解

IF 1.3 4区生物学

Genes to Cells Pub Date : 2025-06-10 DOI: 10.1111/gtc.70032

Seyed Mehdi Hoseini, Farnoosh Moghimi, Elham Sadat Hosseini, Seyed Mohsen Miresmaeili, Mohammad Yahya Vahidi Mehrjardi, Mohammadreza Dehghani, Mohammad Hasan Sheikhha, Fateme Montazeri

{"title":"Microenvironment-Dependent MSC Immunoregulation in Type 1 Diabetes: Insights From IFNγ Preconditioning","authors":"Seyed Mehdi Hoseini, Farnoosh Moghimi, Elham Sadat Hosseini, Seyed Mohsen Miresmaeili, Mohammad Yahya Vahidi Mehrjardi, Mohammadreza Dehghani, Mohammad Hasan Sheikhha, Fateme Montazeri","doi":"10.1111/gtc.70032","DOIUrl":"https://doi.org/10.1111/gtc.70032","url":null,"abstract":"<div>\u0000 \u0000 Interferon-gamma (IFNγ) plays a crucial role in the pathogenesis of type 1 diabetes (T1D) and is widely utilized to license mesenchymal stem/stromal cells (MSCs) to enhance their immunosuppressive properties through a process known as preconditioning or priming. This study investigates the interaction of MSCs preconditioned with (IFNγ+) or without (IFNγ−) IFNγ, with peripheral blood mononuclear cells (PBMCs) from healthy controls (HC) and T1D patients. We assessed the effects of these interactions on anti-inflammatory gene expression, chemokine and receptor profiles, and the induction of regulatory T (Treg) cells. Our findings reveal contrasting responses in HC and T1D PBMCs when exposed to IFNγ+ and IFNγ− MSCs, particularly in the expression of key genes such as CXCR3 and its ligands (CXCL9, CXCL10), CXCR6, CCR5, and its ligands (CCL3 and CCL4). Pathway enrichment analysis further showed that IFNγ preconditioning tailors MSC responses to specific immune microenvironments. These differential gene expression patterns were also reflected in the proportions of Treg cells, which varied depending on whether paracrine signaling or direct cell contact was involved. Collectively, our results demonstrate that IFNγ+ and IFNγ− MSCs create distinct immunomodulatory microenvironments in T1D PBMCs compared to HC PBMCs, emphasizing the potential for tailored MSC-based therapies in T1D treatment.\u0000 </div>","PeriodicalId":12742,"journal":{"name":"Genes to Cells","volume":"30 4","pages":""},"PeriodicalIF":1.3,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144244588","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Aqueous Two-Phase System (ATPS)-Based Spore Isolation in Schizosaccharomyces pombe Requires Isp3-Dependent Surface Hydrophobicity 基于水两相体系（ATPS）的裂糖菌孢子分离需要依赖isp3的表面疏水性

IF 1.3 4区生物学

Genes to Cells Pub Date : 2025-06-02 DOI: 10.1111/gtc.70029

Kazuki Imada

{"title":"Aqueous Two-Phase System (ATPS)-Based Spore Isolation in Schizosaccharomyces pombe Requires Isp3-Dependent Surface Hydrophobicity","authors":"Kazuki Imada","doi":"10.1111/gtc.70029","DOIUrl":"https://doi.org/10.1111/gtc.70029","url":null,"abstract":"<div>\u0000 \u0000 The fission yeast Schizosaccharomyces pombe is a valuable unicellular model organism that proliferates predominantly in the haploid state. Under nitrogen starvation, sexual reproduction occurs, resulting in the formation of a diploid zygote and subsequent meiosis, producing four haploid ascospores. The genetic tractability of yeast, particularly, its ability to produce offspring through sexual reproduction, makes it a widely used model organism. Spores also serve as a model for dormant cells. In this study, I present a highly efficient and low-cost method for purifying S. pombe spores using an aqueous two-phase system (ATPS). Using polyethylene glycol (PEG)-salt (e.g., phosphate)-based ATPS, free spores were found to partition exclusively into the upper (PEG-rich) phase. In contrast, spores lacking Isp3, which forms the outermost spore wall layer, partitioned into the lower (salt-rich) phase, like vegetative cells. This suggests that the Isp3 layer imparts hydrophobicity to the spore surface, facilitating efficient separation in ATPS. This unique surface property may also reflect differences in ecological adaptation and spore dispersal strategies between S. pombe and other fission yeast species.\u0000 </div>","PeriodicalId":12742,"journal":{"name":"Genes to Cells","volume":"30 4","pages":""},"PeriodicalIF":1.3,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144190876","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

PRMT4/CARM1 Is a Novel Factor Promoting DNA Double-Strand Break Repair PRMT4/CARM1是促进DNA双链断裂修复的新因子

IF 1.3 4区生物学

Genes to Cells Pub Date : 2025-06-02 DOI: 10.1111/gtc.70031

Yurina Abe, Hayaki Ikegame, Yuina Tsuchiya, Ryotaro Nishi

{"title":"PRMT4/CARM1 Is a Novel Factor Promoting DNA Double-Strand Break Repair","authors":"Yurina Abe, Hayaki Ikegame, Yuina Tsuchiya, Ryotaro Nishi","doi":"10.1111/gtc.70031","DOIUrl":"https://doi.org/10.1111/gtc.70031","url":null,"abstract":"<div>\u0000 \u0000 DNA double-strand breaks (DSBs), among the most deleterious forms of DNA damage, are primarily repaired by non-homologous end-joining or homologous recombination repair in mammalian cells. Although DSB repair is regulated by various posttranslational modifications, such as phosphorylation, the contribution of protein arginine methylation, catalyzed by protein arginine N-methyltransferases (PRMTs), is less understood. To explore this, we conducted a screen of human PRMTs for their recruitment to the DSB sites in living cells. Among the hits, PRMT4 (also known as coactivator-associated arginine methyltransferase 1: CARM1) was found to accumulate at the DSB sites within 1 min, with the signal dissipating by 10 min post-damage. Further analysis revealed that PRMT4 recruitment to DSB sites depended on its interaction with PARP1, in which both N- and C-terminal domains of PRMT4 were required. In addition, the catalytic activity of PRMT4 was indispensable for releasing PRMT4 from the DSB sites. Finally, the PRMT4 knockout cell line exhibited delayed DSB repair, as evidenced by the neutral comet assay. Consistently, this cell line displayed a higher residual γH2AX signal compared to the parental cells following phleomycin treatment. Collectively, our findings extend the list of PRMTs involved in maintaining genome integrity and identify PRMT4 as a novel factor promoting DSB repair.\u0000 </div>","PeriodicalId":12742,"journal":{"name":"Genes to Cells","volume":"30 4","pages":""},"PeriodicalIF":1.3,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144190875","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Dissection of Behavioral Components and the Role of Omega/Delta Turns for the Chemotaxis of C. elegans 秀丽隐杆线虫行为成分的剖析及Omega/Delta匝在趋化性中的作用

IF 1.3 4区生物学

Genes to Cells Pub Date : 2025-05-29 DOI: 10.1111/gtc.70026

Karin Suwazono, Koyo Kuze, Ukyo T. Tazawa, Moon Sun Jang, Hirofumi Kunitomo, Yu Toyoshima, Yuichi Iino

{"title":"Dissection of Behavioral Components and the Role of Omega/Delta Turns for the Chemotaxis of C. elegans","authors":"Karin Suwazono, Koyo Kuze, Ukyo T. Tazawa, Moon Sun Jang, Hirofumi Kunitomo, Yu Toyoshima, Yuichi Iino","doi":"10.1111/gtc.70026","DOIUrl":"https://doi.org/10.1111/gtc.70026","url":null,"abstract":"The chemotactic mechanism of the nematode Caenorhabditis elegans primarily consists of two components: the pirouette mechanism and the weathervane mechanism. The pirouette mechanism is a form of klinokinesis that regulates the frequency of rapid reorientation behaviors called pirouettes, which include omega/delta turns, while the weathervane mechanism involves gradual directional adjustments. Furthermore, previous studies have shown that in pirouettes, not only is the frequency of reorientation regulated, but the reorientation angle is also adjusted. However, conventional centroid-based analyses have left the postural dynamics during turns unresolved. In this study, we tracked the movement of individual worms during chemotaxis and determined the centerlines representing worm postures. From these data, we extracted turning behaviors, classified postural patterns, and quantified directional changes during turns. Our results indicate that the reorientation angle is modulated during turns to orient the animal toward the desired chemical concentrations. Additionally, we found the diversity of postural dynamics and directional changes in turn sequences. A detailed classification of turn sequences revealed that directional turning is achieved by selection of specific sequence types and adjustment of turning angles. This study provides the most detailed and quantitative analysis to date of the turning behaviors as a fundamental component of C. elegans chemotaxis.","PeriodicalId":12742,"journal":{"name":"Genes to Cells","volume":"30 4","pages":""},"PeriodicalIF":1.3,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/gtc.70026","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144171226","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Generation of Odorant Receptor-QF2 Knock-In Drivers for Improved Analysis of Olfactory Circuits in Drosophila 气味受体qf2敲入驱动因子的产生改善了果蝇嗅觉回路的分析

IF 1.3 4区生物学

Genes to Cells Pub Date : 2025-05-29 DOI: 10.1111/gtc.70028

Yumiko Ukita, Ryoka Suzuki, Keita Miyoshi, Kuniaki Saito, Misako Okumura, Takahiro Chihara

{"title":"Generation of Odorant Receptor-QF2 Knock-In Drivers for Improved Analysis of Olfactory Circuits in Drosophila","authors":"Yumiko Ukita, Ryoka Suzuki, Keita Miyoshi, Kuniaki Saito, Misako Okumura, Takahiro Chihara","doi":"10.1111/gtc.70028","DOIUrl":"https://doi.org/10.1111/gtc.70028","url":null,"abstract":"Drosophila melanogaster has provided numerous insights into the olfactory system, primarily relying on a series of transgenic Gal4 drivers. The combined use of Gal4/UAS and a second binary expression system, such as the QF/QUAS system, provides the opportunity to manipulate the two distinct cell populations, thereby accelerating the elucidation of the olfactory neural mechanisms. However, resources apart from the Gal4/UAS system have been poorly developed. In this study, we generated a series of odorant receptor (Or)-QF2 knock-in driver (Or-QF2KI) lines for 23 Ors using the CRISPR/Cas9 knock-in method. In these lines, the QF2 protein is cotranslated with each Or product. The expression pattern of the Or-QF2KI drivers mostly corresponded to that of the Or-Gal4 drivers. In addition, the Or42a-QF2KI driver identified the additional expression pattern of Or42a, which is consistent with the data of single-nucleus RNA sequencing and is attributed to the Or-QF2KI drivers' ability to reflect the endogenous expression of the Or genes. Thus, these Or-QF2KI drivers can be used as valuable genetic tools for olfactory research in Drosophila.","PeriodicalId":12742,"journal":{"name":"Genes to Cells","volume":"30 4","pages":""},"PeriodicalIF":1.3,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/gtc.70028","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144171227","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Fertilizable Rat Sperm Is Generated in Mice Using Blastocyst Complementation: An Efficient Method for Producing Rats With ES Cell Traits 利用囊胚互补在小鼠体内产生可受精的大鼠精子：一种产生具有胚胎干细胞特征的大鼠的有效方法

IF 1.3 4区生物学

Genes to Cells Pub Date : 2025-05-22 DOI: 10.1111/gtc.70024

Rie Natsume, Kosuke Murata, Hiroaki Taketsuru, Runa Hirayama, Tsugumi Iwasaki, Hideaki Yamashiro, Keizo Takao, Ena Nakatsukasa, Manabu Abe, Kenji Sakimura

{"title":"Fertilizable Rat Sperm Is Generated in Mice Using Blastocyst Complementation: An Efficient Method for Producing Rats With ES Cell Traits","authors":"Rie Natsume, Kosuke Murata, Hiroaki Taketsuru, Runa Hirayama, Tsugumi Iwasaki, Hideaki Yamashiro, Keizo Takao, Ena Nakatsukasa, Manabu Abe, Kenji Sakimura","doi":"10.1111/gtc.70024","DOIUrl":"https://doi.org/10.1111/gtc.70024","url":null,"abstract":"<div>\u0000 \u0000 We developed a novel approach for generating rat offspring using rat embryonic stem (ES) cell-derived sperm produced in mice with the blastocyst complementation method. By optimizing culture conditions, we established naïve male rat ES cells from two transgenic rat strains expressing EGFP and Venus fluorescence, respectively. The pluripotency of these cells was confirmed by the formation of germline chimeras. These ES cells were then injected into blastocysts of germ cell-deficient mice, which resulted in chimeric mice with the ability to produce rat-derived sperm. Histological analysis confirmed the presence of seminiferous tubules and spermatozoa, which are morphologically characteristic of rats, in the chimeric testes. To evaluate the fertilization potential of the chimeric mouse sperm, we performed intracytoplasmic sperm injection (ICSI) to rat oocytes and successfully produced viable offspring carrying ES cell-derived traits. This method eliminates concerns regarding host cell contribution, as all sperm in the chimeras originate from rats, enabling the use of nonfluorescent cells. Furthermore, the absence of competition with host cells is expected to enhance sperm production efficiency. By utilizing germ cell-deficient mice as recipients, this approach offers a cost-effective and efficient strategy for generating genetically modified rats, addressing key limitations in rat ES cell-based genetic engineering.\u0000 </div>","PeriodicalId":12742,"journal":{"name":"Genes to Cells","volume":"30 3","pages":""},"PeriodicalIF":1.3,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144108904","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Alternative Splicing of FBLN2 Generates a Prometastatic Extracellular Matrix in Gastrointestinal Cancers by Determining N-Glycosylation of Fibulin 2 FBLN2的选择性剪接通过决定纤维蛋白2的n -糖基化在胃肠道肿瘤中产生前转移细胞外基质

IF 1.3 4区生物学

Genes to Cells Pub Date : 2025-05-21 DOI: 10.1111/gtc.70027

Ryo Funayama, Yujue Wang, Masaki Hosogane, Wei-Chen Kao, Shingo Toyama, Masahiro Ohira, Masaki Matsumoto, Takashi Aizawa, Minoru Kobayashi, Hideaki Karasawa, Shinobu Ohnuma, Keiichi I. Nakayama, Michiaki Unno, Keiko Nakayama

{"title":"Alternative Splicing of FBLN2 Generates a Prometastatic Extracellular Matrix in Gastrointestinal Cancers by Determining N-Glycosylation of Fibulin 2","authors":"Ryo Funayama, Yujue Wang, Masaki Hosogane, Wei-Chen Kao, Shingo Toyama, Masahiro Ohira, Masaki Matsumoto, Takashi Aizawa, Minoru Kobayashi, Hideaki Karasawa, Shinobu Ohnuma, Keiichi I. Nakayama, Michiaki Unno, Keiko Nakayama","doi":"10.1111/gtc.70027","DOIUrl":"https://doi.org/10.1111/gtc.70027","url":null,"abstract":"Fibulin 2 (FBLN2) is an extracellular matrix glycoprotein. Exclusion of exon 9 of FBLN2 is one of the most recurrent splicing events across multiple types of cancer, but its functional relevance in cancer has remained unexplored. We here reveal that the exclusion of exon 9 of FBLN2 results in the loss of a single N-glycosylation site that leads to misfolding of the FBLN2 protein as well as to a reduction in both its stability and secretion efficiency. Indeed, the extracellular matrix of human colorectal cancer tissue exhibits a reduced abundance of FBLN2. This deficiency of FBLN2 together with a concomitant increase in the abundance of fibronectin 1 in the tumor microenvironment promotes the adhesion and migration of colorectal cancer cells. Our data thus suggest that the alternative splicing of FBLN2 exon 9 generates a prometastatic extracellular environment in cancer tissue by determining FBLN2 glycosylation.","PeriodicalId":12742,"journal":{"name":"Genes to Cells","volume":"30 3","pages":""},"PeriodicalIF":1.3,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/gtc.70027","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144108839","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Polished Rice Regulates Maturation but Not Survival of Secondary Cells in Drosophila Male Accessory Gland 精米调节果蝇雄性副腺次生细胞成熟但不影响其存活

IF 1.3 4区生物学

Genes to Cells Pub Date : 2025-05-10 DOI: 10.1111/gtc.70025

Shinichi Otsune, Mirai Matsuka, Chisato Shirakashi, Xuanshuo Zhang, Hideki Nakagoshi

引用次数: 0

Profiling of RBM20-Regulated CaMKIIδ Splice Variants Across the Heart, Skeletal Muscle, and Olfactory Bulbs 心脏、骨骼肌和嗅球中rbm20调控的CaMKIIδ剪接变异的分析

IF 1.3 4区生物学

Genes to Cells Pub Date : 2025-05-08 DOI: 10.1111/gtc.70021

Yui Maeda, Yuri Yamasu, Hidehito Kuroyanagi

{"title":"Profiling of RBM20-Regulated CaMKIIδ Splice Variants Across the Heart, Skeletal Muscle, and Olfactory Bulbs","authors":"Yui Maeda, Yuri Yamasu, Hidehito Kuroyanagi","doi":"10.1111/gtc.70021","DOIUrl":"https://doi.org/10.1111/gtc.70021","url":null,"abstract":"Calcium/calmodulin-dependent protein kinase IIδ (CaMKIIδ), encoded by the Camk2d gene, plays key regulatory roles in various Ca2+-regulated cellular processes. Extensive alternative splicing of the Camk2d gene generates multiple CaMKIIδ splice variants that exhibit differential roles. Despite significant advances in understanding the functions of CaMKIIδ, the full repertoire of Camk2d splice variants in a variety of tissues and their distinct roles in physiological and pathological contexts remain incompletely characterized due to the complex nature of multiple alternative splicing events. Here, we conducted long-read amplicon sequencing to investigate the murine Camk2d splice variants in the heart, skeletal muscle, and olfactory bulbs and show that mRNAs in the heart and skeletal muscle have shorter 3'UTRs. Our results in this study suggest that a key regulator of Camk2d splicing, RNA-binding motif protein 20 (RBM20), whose gain-of-function mutations cause dilated cardiomyopathy, is crucial for the expression of heart-specific splice variants. Olfactory bulbs specifically express novel splice variants that utilize a mutually exclusive exon 6B and/or an alternative polyadenylation site in a novel exon 17.5 in an RBM20-independent manner. The tissue-specific repertoire of CaMKIIδ splice variants and their aberrant expression in disease model animals will help in understanding their roles in physiological and pathological contexts.","PeriodicalId":12742,"journal":{"name":"Genes to Cells","volume":"30 3","pages":""},"PeriodicalIF":1.3,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/gtc.70021","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143919398","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0