Cell structure and function最新文献_第6页

Munc13b stimulus-dependently accumulates on granuphilin-mediated, docked granules prior to fusion. Munc13b刺激依赖性地在融合前积聚在颗粒蛋白介导的停靠颗粒上。

IF 1.5 4区生物学

Cell structure and function Pub Date : 2022-05-21 Epub Date: 2022-04-06 DOI: 10.1247/csf.22005

Kouichi Mizuno, Tetsuro Izumi

{"title":"Munc13b stimulus-dependently accumulates on granuphilin-mediated, docked granules prior to fusion.","authors":"Kouichi Mizuno, Tetsuro Izumi","doi":"10.1247/csf.22005","DOIUrl":"10.1247/csf.22005","url":null,"abstract":"The Rab27 effector granuphilin plays an indispensable role in stable docking of secretory granules to the plasma membrane by interacting with the complex of Munc18-1 and the fusion-incompetent, closed form of syntaxins-1~3. Although this process prevents spontaneous granule exocytosis, those docked granules actively fuse in parallel with other undocked granules after stimulation. Therefore, it is postulated that the closed form of syntaxins must be converted into the fusion-competent open form in a stimulus-dependent manner. Although Munc13 family proteins are generally thought to prime docked vesicles by facilitating conformational change in syntaxins, it is unknown which isoform acts in granuphilin-mediated, docked granule exocytosis. In the present study, we show that, although both Munc13a and Munc13b are expressed in mouse pancreatic islets and their beta-cell line MIN6, the silencing of Munc13b, but not that of Munc13a, severely affects glucose-induced insulin secretion. Furthermore, Munc13b accumulates on a subset of granules beneath the plasma membrane just prior to fusion during stimulation, whereas Munc13a is translocated to the plasma membrane where granules do not exist. When fluorescently labeled granuphilin was introduced to discriminate between molecularly docked granules and other undocked granules in living cells, Munc13b downregulation was observed to preferentially decrease the fusion of granuphilin-positive granules immobilized to the plasma membrane. These findings suggest that Munc13b promotes insulin exocytosis by clustering on molecularly docked granules in a stimulus-dependent manner.Key words: docking, insulin, live cell imaging, priming, TIRF microscopy.","PeriodicalId":9927,"journal":{"name":"Cell structure and function","volume":"1 1","pages":"31-41"},"PeriodicalIF":1.5,"publicationDate":"2022-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10511056/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45709465","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: 3

Specific association of TBK1 with the trans-Golgi network following STING stimulation. STING 刺激后，TBK1 与跨高尔基体网络的特异性关联。

IF 1.5 4区生物学

Cell structure and function Pub Date : 2022-03-08 Epub Date: 2022-02-05 DOI: 10.1247/csf.21080

Haruka Kemmoku, Yoshihiko Kuchitsu, Kojiro Mukai, Tomohiko Taguchi

{"title":"Specific association of TBK1 with the trans-Golgi network following STING stimulation.","authors":"Haruka Kemmoku, Yoshihiko Kuchitsu, Kojiro Mukai, Tomohiko Taguchi","doi":"10.1247/csf.21080","DOIUrl":"10.1247/csf.21080","url":null,"abstract":"Stimulator of interferon genes (STING) is essential for the type I interferon response induced by microbial DNA or self-DNA leaked from mitochondria/nuclei. In response to the emergence of such DNAs in the cytosol, STING relocates from the endoplasmic reticulum (ER) to the Golgi, and activates TANK-binding kinase 1 (TBK1), a cytosolic kinase essential for the activation of STING-dependent downstream signalling. To understand at which subcellular compartments TBK1 becomes associated with STING, we generated cells stably expressing fluorescent protein-tagged STING (mNeonGreen-STING) and TBK1 (TBK1-mScarletI). We found that after STING stimulation, TBK1 became associated with the trans-Golgi network (TGN), not the other parts of the Golgi. STING variants that constitutively induce the type I interferon response have been identified in patients with autoinflammatory diseases named \"STING-associated vasculopathy with onset in infancy (SAVI)\". Even in cells expressing these constitutively active STING variants, TBK1 was found to be associated with TGN, not the other parts of the Golgi. These results suggest that TGN acts as a specific platform where STING associates with and activates TBK1.Key words: the Golgi, membrane traffic, innate immunity, STING.","PeriodicalId":9927,"journal":{"name":"Cell structure and function","volume":"47 1","pages":"19-30"},"PeriodicalIF":1.5,"publicationDate":"2022-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10511044/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39893250","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: 5

Ubiquitin-like 3 as a new protein-sorting factor for small extracellular vesicles. 类泛素 3 是一种新的细胞外小囊泡蛋白质分类因子。

IF 1.5 4区生物学

Cell structure and function Pub Date : 2022-01-01 DOI: 10.1247/csf.21078

Yusuke Takanashi, Tomoaki Kahyo, Sae Kamamoto, Hengsen Zhang, Bin Chen, Yashuang Ping, Kiyomichi Mizuno, Akikazu Kawase, Kei Koizumi, Masanori Satou, Kazuhito Funai, Norihiko Shiiya, Mitsutoshi Setou

{"title":"Ubiquitin-like 3 as a new protein-sorting factor for small extracellular vesicles.","authors":"Yusuke Takanashi, Tomoaki Kahyo, Sae Kamamoto, Hengsen Zhang, Bin Chen, Yashuang Ping, Kiyomichi Mizuno, Akikazu Kawase, Kei Koizumi, Masanori Satou, Kazuhito Funai, Norihiko Shiiya, Mitsutoshi Setou","doi":"10.1247/csf.21078","DOIUrl":"10.1247/csf.21078","url":null,"abstract":"Ubiquitin-like 3 (UBL3) is a well-conserved ubiquitin-like protein (UBL) in eukaryotes and regulates the ubiquitin cascade, but the significant roles of UBL3 in cellular processes remained unknown. Recently, UBL3 was elucidated to be a post-translational modification factor that promotes protein sorting to small extracellular vesicles (sEVs). Proteins sorted into sEVs have been studied as etiologies of sEV-related diseases. Also, there have been attempts to construct drug delivery systems (DDSs) by loading proteins into sEVs. In this review, we introduce the new concept that UBL3 has a critical role in the protein-sorting system and compare structure conservation between UBL3 and other UBLs from an evolutionary perspective. We conclude with future perspectives for the utility of UBL3 in sEV-related diseases and DDS.Key words: UBL3, small extracellular vesicles, protein sorting, ubiquitin-like protein, post-translational modification.","PeriodicalId":9927,"journal":{"name":"Cell structure and function","volume":"47 1","pages":"1-18"},"PeriodicalIF":1.5,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10511055/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39658267","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: 2

A Dual Promoter System to Monitor IFN-γ Signaling in vivo at Single-cell Resolution. 以单细胞分辨率监测体内 IFN-γ 信号的双启动子系统

IF 1.5 4区生物学

Cell structure and function Pub Date : 2021-12-22 Epub Date: 2021-11-06 DOI: 10.1247/csf.21052

Taisei Tanaka, Yoshinobu Konishi, Hiroshi Ichise, Shinya Tsukiji, Michiyuki Matsuda, Kenta Terai

{"title":"A Dual Promoter System to Monitor IFN-γ Signaling in vivo at Single-cell Resolution.","authors":"Taisei Tanaka, Yoshinobu Konishi, Hiroshi Ichise, Shinya Tsukiji, Michiyuki Matsuda, Kenta Terai","doi":"10.1247/csf.21052","DOIUrl":"10.1247/csf.21052","url":null,"abstract":"IFN-γ secreted from immune cells exerts pleiotropic effects on tumor cells, including induction of immune checkpoint and antigen presentation, growth inhibition, and apoptosis induction. We combined a dual promoter system with an IFN-γ signaling responsive promoter to generate a reporter named the interferon sensing probe (ISP), which quantitates the response to IFN-γ by means of fluorescence and bioluminescence. The integration site effect of the transgene is compensated for by the PGK promoter-driven expression of a fluorescent protein. Among five potential IFN-γ-responsive elements, we found that the interferon γ-activated sequence (GAS) exhibited the best performance. When ISP-GAS was introduced into four cell lines and subjected to IFN-γ stimulation, dose-dependency was observed with an EC50 ranging from 0.2 to 0.9 ng/mL, indicating that ISP-GAS can be generally used as a sensitive biosensor of IFN-γ response. In a syngeneic transplantation model, the ISP-GAS-expressing cancer cells exhibited bioluminescence and fluorescence signals in an IFN-γ receptor-dependent manner. Thus, ISP-GAS could be used to quantitatively monitor the IFN-γ response both in vitro and in vivo.Key words: in vivo imaging, tumor microenvironment, interferon-gamma, dual promoter system.","PeriodicalId":9927,"journal":{"name":"Cell structure and function","volume":"46 2","pages":"103-111"},"PeriodicalIF":1.5,"publicationDate":"2021-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10511040/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39596761","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: 1

Visualization of DNA Replication in Single Chromosome by Stable Isotope Labeling. 通过稳定同位素标记观察单个染色体中的 DNA 复制。

IF 1.5 4区生物学

Cell structure and function Pub Date : 2021-11-20 Epub Date: 2021-09-25 DOI: 10.1247/csf.21011

Kosuke Nagata, Ken-Ichi Bajo, Hideyuki Mitomo, Ryosuke Fujita, Ryota Uehara, Kuniharu Ijiro, Hisayoshi Yurimoto

引用次数: 0

Nuclear RNA Regulation by XRN2 and XTBD Family Proteins. XRN2 和 XTBD 家族蛋白对核 RNA 的调控

IF 1.5 4区生物学

Cell structure and function Pub Date : 2021-11-06 Epub Date: 2021-09-03 DOI: 10.1247/csf.21041

Ilkin Aygün, Takashi S Miki

引用次数: 0

In vivo Roles of Rab27 and Its Effectors in Exocytosis. Rab27 及其效应因子在体内外吞过程中的作用

IF 1.5 4区生物学

Cell structure and function Pub Date : 2021-11-06 Epub Date: 2021-09-04 DOI: 10.1247/csf.21043

Tetsuro Izumi

{"title":"In vivo Roles of Rab27 and Its Effectors in Exocytosis.","authors":"Tetsuro Izumi","doi":"10.1247/csf.21043","DOIUrl":"10.1247/csf.21043","url":null,"abstract":"The monomeric GTPase Rab27 regulates exocytosis of a broad range of vesicles in multicellular organisms. Several effectors bind GTP-bound Rab27a and/or Rab27b on secretory vesicles to execute a series of exocytic steps, such as vesicle maturation, movement along microtubules, anchoring within the peripheral F-actin network, and tethering to the plasma membrane, via interactions with specific proteins and membrane lipids in a local milieu. Although Rab27 effectors generally promote exocytosis, they can also temporarily restrict it when they are involved in the rate-limiting step. Genetic alterations in Rab27-related molecules cause discrete diseases manifesting pigment dilution and immunodeficiency, and can also affect common diseases such as diabetes and cancer in complex ways. Although the function and mechanism of action of these effectors have been explored, it is unclear how multiple effectors act in coordination within a cell to regulate the secretory process as a whole. It seems that Rab27 and various effectors constitutively reside on individual vesicles to perform consecutive exocytic steps. The present review describes the unique properties and in vivo roles of the Rab27 system, and the functional relationship among different effectors coexpressed in single cells, with pancreatic beta cells used as an example.Key words: membrane trafficking, regulated exocytosis, insulin granules, pancreatic beta cells.","PeriodicalId":9927,"journal":{"name":"Cell structure and function","volume":"46 2","pages":"79-94"},"PeriodicalIF":1.5,"publicationDate":"2021-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10511049/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39384597","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: 1

Hrd1-dependent Degradation of the Unassembled PIGK Subunit of the GPI Transamidase Complex. 依赖于 Hrd1 的 GPI 跨酰胺酶复合物未组装 PIGK 亚基降解。

IF 1.5 4区生物学

Cell structure and function Pub Date : 2021-09-03 Epub Date: 2021-06-30 DOI: 10.1247/csf.21019

Kohei Kawaguchi, Miki Yamamoto-Hino, Yoshiko Murakami, Taroh Kinoshita, Satoshi Goto

引用次数: 1

Expression Patterns and Levels of All Tubulin Isotypes Analyzed in GFP Knock-In C. elegans Strains. 在 GFP 基因敲入 C. elegans 株系中分析的所有微管蛋白异型的表达模式和水平。

IF 2 4区生物学

Cell structure and function Pub Date : 2021-06-30 Epub Date: 2021-05-08 DOI: 10.1247/csf.21022

Kei Nishida, Kenta Tsuchiya, Hiroyuki Obinata, Shizuka Onodera, Yu Honda, Yen-Cheng Lai, Nami Haruta, Asako Sugimoto

{"title":"Expression Patterns and Levels of All Tubulin Isotypes Analyzed in GFP Knock-In C. elegans Strains.","authors":"Kei Nishida, Kenta Tsuchiya, Hiroyuki Obinata, Shizuka Onodera, Yu Honda, Yen-Cheng Lai, Nami Haruta, Asako Sugimoto","doi":"10.1247/csf.21022","DOIUrl":"10.1247/csf.21022","url":null,"abstract":"Most organisms have multiple α- and β-tubulin isotypes that likely contribute to the diversity of microtubule (MT) functions. To understand the functional differences of tubulin isotypes in Caenorhabditis elegans, which has nine α-tubulin isotypes and six β-tubulin isotypes, we systematically constructed null mutants and GFP-fusion strains for all tubulin isotypes with the CRISPR/Cas9 system and analyzed their expression patterns and levels in adult hermaphrodites. Four isotypes-α-tubulins TBA-1 and TBA-2 and β-tubulins TBB-1 and TBB-2-were expressed in virtually all tissues, with a distinct tissue-specific spectrum. Other isotypes were expressed in specific tissues or cell types at significantly lower levels than the broadly expressed isotypes. Four isotypes (TBA-5, TBA-6, TBA-9, and TBB-4) were expressed in different subsets of ciliated sensory neurons, and TBB-4 was inefficiently incorporated into mitotic spindle MTs. Taken together, we propose that MTs in C. elegans are mainly composed of four broadly expressed tubulin isotypes and that incorporation of a small amount of tissue-specific isotypes may contribute to tissue-specific MT properties. These newly constructed strains will be useful for further elucidating the distinct roles of tubulin isotypes.Key words: tubulin isotypes, microtubules, C. elegans.","PeriodicalId":9927,"journal":{"name":"Cell structure and function","volume":"46 1","pages":"51-64"},"PeriodicalIF":2.0,"publicationDate":"2021-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10511039/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38883723","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

Multiple Ways for Stress Sensing and Regulation of the Endoplasmic Reticulum-stress Sensors. 内质网应力传感器的多种应力感应和调节方式

IF 2 4区生物学

Cell structure and function Pub Date : 2021-05-22 Epub Date: 2021-03-26 DOI: 10.1247/csf.21015

Quynh Giang Le, Yukio Kimata

{"title":"Multiple Ways for Stress Sensing and Regulation of the Endoplasmic Reticulum-stress Sensors.","authors":"Quynh Giang Le, Yukio Kimata","doi":"10.1247/csf.21015","DOIUrl":"10.1247/csf.21015","url":null,"abstract":"Dysfunction of the endoplasmic reticulum (ER), so-called ER stress, is accompanied with accumulation of unfolded proteins in the ER. Eukaryotic cells commonly have an ER-located transmembrane protein, Ire1, which triggers cellular protective events against ER stress. In animal cells, PERK and ATF6 also initiate the ER-stress response. As a common strategy to control the activity of these ER-stress sensors, an ER-resident molecular chaperone, BiP, serves as their negative regulator, and dissociates from them in response to ER stress. Although it sounds reasonable that unfolded proteins and Ire1 compete for BiP association, some publications argue against this competition model. Moreover, yeast Ire1 (and possibly also the mammalian major Ire1 paralogue IRE1α) directly detects ER-accumulated unfolded proteins, and subsequently oligomerizes for its further activation. Apart from protein misfolding, the saturation of membrane phospholipids is another outcome of ER-stressing stimuli, which is sensed by the transmembrane domain of Ire1. This review describes the canonical and up-to-date insights concerning stress-sensing and regulatory mechanisms of yeast Ire1 and metazoan ER-stress sensors.Key words: endoplasmic reticulum, stress, unfolded protein response, molecular chaperone.","PeriodicalId":9927,"journal":{"name":"Cell structure and function","volume":"46 1","pages":"37-49"},"PeriodicalIF":2.0,"publicationDate":"2021-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10511038/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25537938","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