Genes to Cells最新文献_第9页

Extracellular α-synuclein impairs sphingosine 1-phosphate receptor type 3 (S1PR3)-regulated lysosomal delivery of cathepsin D in HeLa cells 细胞外的α-突触核蛋白会损害HeLa细胞中由1-磷酸鞘氨醇受体3型（S1PR3）调控的溶酶体中猫毒素D的输送。

IF 2.1 4区生物学

Genes to Cells Pub Date : 2024-01-01 DOI: 10.1111/gtc.13093

Susumu Nishida, Shubi Ambwene Matovelo, Taketoshi Kajimoto, Shun-ichi Nakamura, Taro Okada

{"title":"Extracellular α-synuclein impairs sphingosine 1-phosphate receptor type 3 (S1PR3)-regulated lysosomal delivery of cathepsin D in HeLa cells","authors":"Susumu Nishida, Shubi Ambwene Matovelo, Taketoshi Kajimoto, Shun-ichi Nakamura, Taro Okada","doi":"10.1111/gtc.13093","DOIUrl":"10.1111/gtc.13093","url":null,"abstract":"α-Synuclein (α-Syn)-positive intracellular fibrillar protein deposits, known as Lewy bodies, are thought to be involved in the pathogenesis of Parkinson's disease (PD). Although recent lines of evidence suggested that extracellular α-Syn secreted from pathogenic neurons contributes to the propagation of PD pathology, the precise mechanism of action remains unclear. We have reported that extracellular α-Syn caused sphingosine 1-phosphate (S1P) receptor type 1 (S1PR1) uncoupled from Gi and inhibited downstream G-protein signaling in SH-SY5Y cells, although its patho/physiological role remains to be clarified. Here we show that extracellular α-Syn caused S1P receptor type 3 (S1PR3) uncoupled from G protein in HeLa cells. Further studies indicated that α-Syn treatment reduced cathepsin D activity while enhancing the secretion of immature pro-cathepsin D into cell culture medium, suggesting that lysosomal delivery of cathepsin D was disturbed. Actually, extracellular α-Syn attenuated the retrograde trafficking of insulin-like growth factor-II/mannose 6-phosphate (IGF-II/M6P) receptor, which is under the regulation of S1PR3. These findings shed light on the understanding of dissemination of the PD pathology, that is, the mechanism underlying how extracellular α-Syn secreted from pathogenic cells causes lysosomal dysfunction of the neighboring healthy cells, leading to propagation of the disease.","PeriodicalId":12742,"journal":{"name":"Genes to Cells","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139073792","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

Metastatic potentials classified with hypoxia-inducible factor 1 downstream genes in pan-cancer cell lines 根据泛癌细胞系中的低氧诱导因子 1 下游基因对转移潜力进行分类。

IF 2.1 4区生物学

Genes to Cells Pub Date : 2023-12-29 DOI: 10.1111/gtc.13092

Kazuya Nakamichi, Yusuke Yamamoto, Kentaro Semba, Jun Nakayama

引用次数: 0

Generation of inducible mitophagy mice 诱导性有丝分裂小鼠的产生。

IF 2.1 4区生物学

Genes to Cells Pub Date : 2023-12-22 DOI: 10.1111/gtc.13091

Toshiyuki Nishiji, Atsushi Hoshino, Yuki Uchio, Satoaki Matoba

{"title":"Generation of inducible mitophagy mice","authors":"Toshiyuki Nishiji, Atsushi Hoshino, Yuki Uchio, Satoaki Matoba","doi":"10.1111/gtc.13091","DOIUrl":"10.1111/gtc.13091","url":null,"abstract":"Mitophagy is programmed selective autophagy of mitochondria and is important for mitochondrial quality control and cellular homeostasis. Mitochondrial dysfunction and impaired mitophagy are closely associated with various diseases, including heart failure and diabetes. To better understand the pathophysiological role of mitophagy, we generated doxycycline-inducible mitophagy mice using a synthetic mitophagy adaptor protein consisting of an outer mitochondrial membrane targeting sequence and an engineered LIR. To evaluate the activation of mitophagy upon doxycycline treatment, we also generated mitophagy reporter mito-QC mice in which mitochondria tandemly express mCherry and GFP, and only GFP signals are lost in acidic lysosomes subjected to mitophagy. With the ROSA26 promoter-driven rtTA, mitophagy was observed at least in heart, liver, and skeletal muscle. We investigated the relationship between mitophagy activation and pressure overload heart failure or high fat diet-induced obesity. Unexpectedly, we were unable to confirm the protective effect of mitophagy in these two pathological models. Further titration of the level of mitophagy induction is required to demonstrate the potency of the protective effects of mitophagy in disease models.","PeriodicalId":12742,"journal":{"name":"Genes to Cells","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2023-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138829296","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

Insertion sequence excision is enhanced by a protein that catalyzes branch migration and promotes microhomology-mediated end joining 一种能催化分支迁移并促进微结构介导的末端连接的蛋白质能增强插入序列切除功能

IF 2.1 4区生物学

Genes to Cells Pub Date : 2023-12-14 DOI: 10.1111/gtc.13090

Ren Kishino, Takashi Saito, Shuntaro Muto, Yuzuka Tomita, Yasuhiko Sekine

{"title":"Insertion sequence excision is enhanced by a protein that catalyzes branch migration and promotes microhomology-mediated end joining","authors":"Ren Kishino, Takashi Saito, Shuntaro Muto, Yuzuka Tomita, Yasuhiko Sekine","doi":"10.1111/gtc.13090","DOIUrl":"10.1111/gtc.13090","url":null,"abstract":"Insertion sequence (IS)-excision enhancer (IEE) promotes the excision of ISs in the genome of enterohemorrhagic Escherichia coli O157. Because IEE-dependent IS excision occurs in the presence of transposase, the process of IS transposition may be involved in IS excision; however, little is understood about the molecular mechanisms of IS excision. Our in vitro analysis revealed that IEE exhibits DNA-dependent ATPase activity, which is activated by branched DNA. IEE also catalyzes the branch migration of fork-structured DNA. These results suggest that IEE remodels branched structures of the IS transposition intermediate. Sequence analysis of recombination sites in IS-excision products suggested that microhomologous sequences near the ends of the IS are involved in IS excision. IEE promoted microhomology-mediated end joining (MMEJ), in which base pairing between 6-nucleotides complementary ends of two 3′-protruding DNAs and subsequent elongation of the paired DNA strand occurred. IS-excision frequencies were significantly decreased in cells producing IEE mutants that had lost either branch migration or MMEJ activity, which suggests that these activities of IEE are required for IS excision. Based on our results, we propose a model for IS excision triggered by IEE and transposase.","PeriodicalId":12742,"journal":{"name":"Genes to Cells","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2023-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138680466","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

Acidic growth conditions stabilize the ribosomal RNA gene cluster and extend lifespan through noncoding transcription repression 酸性生长条件可稳定核糖体 RNA 基因簇，并通过非编码转录抑制延长寿命

IF 2.1 4区生物学

Genes to Cells Pub Date : 2023-12-08 DOI: 10.1111/gtc.13089

Yo Hasegawa, Hiroyuki Ooka, Tsuyoshi Wakatsuki, Mariko Sasaki, Ayumi Yamamoto, Takehiko Kobayashi

{"title":"Acidic growth conditions stabilize the ribosomal RNA gene cluster and extend lifespan through noncoding transcription repression","authors":"Yo Hasegawa, Hiroyuki Ooka, Tsuyoshi Wakatsuki, Mariko Sasaki, Ayumi Yamamoto, Takehiko Kobayashi","doi":"10.1111/gtc.13089","DOIUrl":"10.1111/gtc.13089","url":null,"abstract":"Blackcurrant (Ribes nigrum L.) is a classical fruit that has long been used to make juice, jam, and liqueur. Blackcurrant extract is known to relieve cells from DNA damage caused by hydrogen peroxide (H2O2), methyl methane sulfonate (MMS), and ultraviolet (UV) radiation. We found that blackcurrant extract (BCE) stabilizes the ribosomal RNA gene cluster (rDNA), one of the most unstable regions in the genome, through repression of noncoding transcription in the intergenic spacer (IGS) which extended the lifespan in budding yeast. Reduced formation of extrachromosomal circles (ERCs) after exposure to fractionated BCE suggested that acidity of the growth medium impacted rDNA stability. Indeed, alteration of the acidity of the growth medium to pH ~4.5 by adding HCl increased rDNA stability and extended the lifespan. We identified RPD3 as the gene responsible for this change, which was mediated by the RPD3L histone deacetylase complex. In mammals, as inflammation sites in a tissue are acidic, DNA maintenance may be similarly regulated to prevent genome instability from causing cancer.","PeriodicalId":12742,"journal":{"name":"Genes to Cells","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2023-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/gtc.13089","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138588312","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

CD271 promotes proliferation and migration in bladder cancer CD271促进膀胱癌的增殖和迁移。

IF 2.1 4区生物学

Genes to Cells Pub Date : 2023-11-28 DOI: 10.1111/gtc.13087

Shingo Myoen, Mai Mochizuki, Rie Shibuya-Takahashi, Haruna Fujimori, Norihisa Shindo, Kazunori Yamaguchi, Jun Yasuda, Jiro Abe, Takayuki Imai, Ikuro Sato, Hisanobu Adachi, Sadafumi Kawamura, Akihiro Ito, Keiichi Tamai

{"title":"CD271 promotes proliferation and migration in bladder cancer","authors":"Shingo Myoen, Mai Mochizuki, Rie Shibuya-Takahashi, Haruna Fujimori, Norihisa Shindo, Kazunori Yamaguchi, Jun Yasuda, Jiro Abe, Takayuki Imai, Ikuro Sato, Hisanobu Adachi, Sadafumi Kawamura, Akihiro Ito, Keiichi Tamai","doi":"10.1111/gtc.13087","DOIUrl":"10.1111/gtc.13087","url":null,"abstract":"Bladder cancer is a urothelial cancer and effective therapeutic strategies for its advanced stages are limited. Here, we report that CD271, a neurotrophin receptor, promotes the proliferation and migration of bladder cancer cells. CD271 knockdown decreased proliferation in both adherent and spheroid cultures, and vice versa when CD271 was overexpressed in bladder cancer cell lines. CD271 depletion impaired tumorigenicity in vivo. Migration activity was reduced by CD271 knockdown and TAT-Pep5, a known CD271-Rho GDI-binding inhibitor. Apoptosis was induced by CD271 knockdown. Comprehensive gene expression analysis revealed alterations in E2F- and Myc-related pathways upon CD271 expression. In clinical cases, patients with high CD271 expression showed significantly shortened overall survival. In surgically resected specimens, pERK, a known player in proliferation signaling, colocalizes with CD271. These data indicate that CD271 is involved in bladder cancer malignancy by promoting cell proliferation and migration, resulting in poor prognosis.","PeriodicalId":12742,"journal":{"name":"Genes to Cells","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2023-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138451301","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

IMPDH2 forms spots at branching sites and distal ends of astrocyte stem processes IMPDH2在星形胶质细胞干突的分支位点和远端形成斑点。

IF 2.1 4区生物学

Genes to Cells Pub Date : 2023-11-27 DOI: 10.1111/gtc.13088

Saori Toyoda, Takehisa Handa, Huang Yong, Hidehiko Takahashi, Hiroki Shiwaku

引用次数: 0

Brain-derived neurotrophic factor (BDNF) downregulates mRNA levels of suppressor of cancer cell invasion (SCAI) variants in cortical neurons 脑源性神经营养因子(BDNF)下调皮层神经元中癌细胞侵袭(SCAI)变体抑制因子的mRNA水平。

IF 2.1 4区生物学

Genes to Cells Pub Date : 2023-11-27 DOI: 10.1111/gtc.13086

Daisuke Ihara, Miho Mizukoshi, Akiko Tabuchi

{"title":"Brain-derived neurotrophic factor (BDNF) downregulates mRNA levels of suppressor of cancer cell invasion (SCAI) variants in cortical neurons","authors":"Daisuke Ihara, Miho Mizukoshi, Akiko Tabuchi","doi":"10.1111/gtc.13086","DOIUrl":"10.1111/gtc.13086","url":null,"abstract":"Suppressor of cancer cell invasion (SCAI) acts as a transcriptional repressor of serum response factor (SRF)-mediated gene expression by binding to megakaryoblastic leukemia (MKL)/myocardin-related transcription factor (MRTF), which is an SRF transcriptional coactivator. Growing evidence suggests that SCAI is a negative regulator of neuronal morphology, whereas MKL2/MRTFB is a positive regulator. The mRNA expression of SCAI is downregulated during brain development, suggesting that a reduction in SCAI contributes to the reduced suppression of SRF-mediated gene induction, thus increasing dendritic complexity and developing neuronal circuits. In the present study, we hypothesized that brain-derived neurotrophic factor (BDNF), which is important for neuronal plasticity and development, might alter SCAI mRNA levels. We therefore investigated the effects of BDNF on SCAI mRNA levels in primary cultured cortical neurons. Furthermore, because alternative splicing generates several SCAI variants in the brain, we measured SCAI variant mRNA after BDNF stimulation. Both SCAI variant 1 and total SCAI mRNA expression levels were downregulated by BDNF. Moreover, the extracellular signal-regulated protein kinase/mitogen-activated protein kinase (ERK/MAPK) pathway was involved in the BDNF-mediated decrease in SCAI mRNA expression. Our findings provide insights into the molecular mechanism underlying a neurotrophic factor switch for the repressive transcriptional complex that includes SCAI.","PeriodicalId":12742,"journal":{"name":"Genes to Cells","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2023-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138444397","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

Visualization of the landscape of the read alignment shape of ATAC-seq data using Hellinger distance metric 基于Hellinger距离度量的ATAC-seq数据读取对齐形状景观可视化

IF 2.1 4区生物学

Genes to Cells Pub Date : 2023-11-21 DOI: 10.1111/gtc.13082

Jian Hao Cheng, Cheng Zheng, Ryo Yamada, Daigo Okada

{"title":"Visualization of the landscape of the read alignment shape of ATAC-seq data using Hellinger distance metric","authors":"Jian Hao Cheng, Cheng Zheng, Ryo Yamada, Daigo Okada","doi":"10.1111/gtc.13082","DOIUrl":"10.1111/gtc.13082","url":null,"abstract":"Assay for Transposase-Accessible Chromatin using high-throughput sequencing (ATAC-seq) is the popular technique using next-generation sequencing to measure chromatin accessibility and identify open chromatin regions. While read alignment shape information of next-generation sequencing data with intensity information has been used in various bioinformatics methods, few studies have focused on pure shape information alone. In this study, we investigated what types of ATAC-seq read alignment shapes are observed for the promoter region and whether the pure shape information was related or unrelated to other gene features. We introduced a novel concept and pipeline for handling the pure shape information of NGS data as probability distributions and quantifying their dissimilarities by information theory. Based on this concept, we demonstrate that the pure shape information of ATAC-seq data is correlated with chromatin openness and some gene characteristics. On the other hand, it is suggested that the pure information of ATAC-seq read alignment shape is unlikely to contain additional information to explain differences in RNA expression. Our study suggests that viewing the read alignment shape of NGS data as probability distributions enables us to capture the characteristics of the genome-wide landscape of such data in a non-parametric manner.","PeriodicalId":12742,"journal":{"name":"Genes to Cells","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2023-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138290781","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

Structural basis of Irgb6 inactivation by Toxoplasma gondii through the phosphorylation of switch I 刚地弓形虫通过开关I磷酸化使Irgb6失活的结构基础

IF 2.1 4区生物学

Genes to Cells Pub Date : 2023-11-20 DOI: 10.1111/gtc.13080

Hiromichi Okuma, Yumiko Saijo-Hamano, Hiroshi Yamada, Aalaa Alrahman Sherif, Emi Hashizaki, Naoki Sakai, Takaaki Kato, Tsuyoshi Imasaki, Satoshi Kikkawa, Eriko Nitta, Miwa Sasai, Tadashi Abe, Fuminori Sugihara, Yoshimasa Maniwa, Hidetaka Kosako, Kohji Takei, Daron M. Standley, Masahiro Yamamoto, Ryo Nitta

{"title":"Structural basis of Irgb6 inactivation by Toxoplasma gondii through the phosphorylation of switch I","authors":"Hiromichi Okuma, Yumiko Saijo-Hamano, Hiroshi Yamada, Aalaa Alrahman Sherif, Emi Hashizaki, Naoki Sakai, Takaaki Kato, Tsuyoshi Imasaki, Satoshi Kikkawa, Eriko Nitta, Miwa Sasai, Tadashi Abe, Fuminori Sugihara, Yoshimasa Maniwa, Hidetaka Kosako, Kohji Takei, Daron M. Standley, Masahiro Yamamoto, Ryo Nitta","doi":"10.1111/gtc.13080","DOIUrl":"10.1111/gtc.13080","url":null,"abstract":"Irgb6 is a priming immune-related GTPase (IRG) that counteracts Toxoplasma gondii. It is known to be recruited to the low virulent type II T. gondii parasitophorous vacuole (PV), initiating cell-autonomous immunity. However, the molecular mechanism by which immunity-related GTPases become inactivated after the parasite infection remains obscure. Here, we found that Thr95 of Irgb6 is prominently phosphorylated in response to low virulent type II T. gondii infection. We observed that a phosphomimetic T95D mutation in Irgb6 impaired its localization to the PV and exhibited reduced GTPase activity in vitro. Structural analysis unveiled an atypical conformation of nucleotide-free Irgb6-T95D, resulting from a conformational change in the G-domain that allosterically modified the PV membrane-binding interface. In silico docking corroborated the disruption of the physiological membrane binding site. These findings provide novel insights into a T. gondii-induced allosteric inactivation mechanism of Irgb6.","PeriodicalId":12742,"journal":{"name":"Genes to Cells","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2023-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/gtc.13080","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138176080","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