Life Science Alliance最新文献

Clonal landscape of autoantibody-secreting plasmablasts in COVID-19 patients. COVID-19 患者自身抗体分泌浆细胞的克隆分布。

IF 4.4 2区生物学

Life Science Alliance Pub Date : 2024-09-17 DOI: 10.26508/lsa.202402774

Shuhei Sakakibara,Yu-Chen Liu,Masakazu Ishikawa,Ryuya Edahiro,Yuya Shirai,Soichiro Haruna,Marwa Ali El Hussien,Zichang Xu,Songling Li,Yuta Yamaguchi,Teruaki Murakami,Takayoshi Morita,Yasuhiro Kato,Haruhiko Hirata,Yoshito Takeda,Fuminori Sugihara,Yoko Naito,Daisuke Motooka,Chao-Yuan Tsai,Chikako Ono,Yoshiharu Matsuura,James B Wing,Hisatake Matsumoto,Hiroshi Ogura,Masato Okada,Atsushi Kumanogoh,Yukinari Okada,Daron M Standley,Hitoshi Kikutani,Daisuke Okuzaki

{"title":"Clonal landscape of autoantibody-secreting plasmablasts in COVID-19 patients.","authors":"Shuhei Sakakibara,Yu-Chen Liu,Masakazu Ishikawa,Ryuya Edahiro,Yuya Shirai,Soichiro Haruna,Marwa Ali El Hussien,Zichang Xu,Songling Li,Yuta Yamaguchi,Teruaki Murakami,Takayoshi Morita,Yasuhiro Kato,Haruhiko Hirata,Yoshito Takeda,Fuminori Sugihara,Yoko Naito,Daisuke Motooka,Chao-Yuan Tsai,Chikako Ono,Yoshiharu Matsuura,James B Wing,Hisatake Matsumoto,Hiroshi Ogura,Masato Okada,Atsushi Kumanogoh,Yukinari Okada,Daron M Standley,Hitoshi Kikutani,Daisuke Okuzaki","doi":"10.26508/lsa.202402774","DOIUrl":"https://doi.org/10.26508/lsa.202402774","url":null,"abstract":"Whereas severe COVID-19 is often associated with elevated autoantibody titers, the underlying mechanism behind their generation has remained unclear. Here we report clonal composition and diversity of autoantibodies in humoral response to SARS-CoV-2. Immunoglobulin repertoire analysis and characterization of plasmablast-derived monoclonal antibodies uncovered clonal expansion of plasmablasts producing cardiolipin (CL)-reactive autoantibodies. Half of the expanded CL-reactive clones exhibited strong binding to SARS-CoV-2 antigens. One such clone, CoV1804, was reactive to both CL and viral nucleocapsid (N), and further showed anti-nucleolar activity in human cells. Notably, antibodies sharing genetic features with CoV1804 were identified in COVID-19 patient-derived immunoglobulins, thereby constituting a novel public antibody. These public autoantibodies had numerous mutations that unambiguously enhanced anti-N reactivity, when causing fluctuations in anti-CL reactivity along with the acquisition of additional self-reactivities, such as anti-nucleolar activity, in the progeny. Thus, potentially CL-reactive precursors may have developed multiple self-reactivities through clonal selection, expansion, and somatic hypermutation driven by viral antigens. Our results revealed the nature of autoantibody production during COVID-19 and provided novel insights into the origin of virus-induced autoantibodies.","PeriodicalId":18081,"journal":{"name":"Life Science Alliance","volume":"50 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142266498","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

Nanoscale imaging of DNA-RNA identifies transcriptional plasticity at heterochromatin. DNA-RNA 的纳米级成像可识别异染色质的转录可塑性。

IF 4.4 2区生物学

Life Science Alliance Pub Date : 2024-09-17 DOI: 10.26508/lsa.202402849

Christelle Guillermier,Naveen Vg Kumar,Ronan C Bracken,Diana Alvarez,John O'Keefe,Aditi Gurkar,Jonathan D Brown,Matthew L Steinhauser

{"title":"Nanoscale imaging of DNA-RNA identifies transcriptional plasticity at heterochromatin.","authors":"Christelle Guillermier,Naveen Vg Kumar,Ronan C Bracken,Diana Alvarez,John O'Keefe,Aditi Gurkar,Jonathan D Brown,Matthew L Steinhauser","doi":"10.26508/lsa.202402849","DOIUrl":"https://doi.org/10.26508/lsa.202402849","url":null,"abstract":"The three-dimensional structure of DNA is a biophysical determinant of transcription. The density of chromatin condensation is one determinant of transcriptional output. Chromatin condensation is generally viewed as enforcing transcriptional suppression, and therefore, transcriptional output should be inversely proportional to DNA compaction. We coupled stable isotope tracers with multi-isotope imaging mass spectrometry to quantify and image nanovolumetric relationships between DNA density and newly made RNA within individual nuclei. Proliferative cell lines and cycling cells in the murine small intestine unexpectedly demonstrated no consistent relationship between DNA density and newly made RNA, even though localized examples of this phenomenon were detected at nuclear-cytoplasmic transitions. In contrast, non-dividing hepatocytes demonstrated global reduction in newly made RNA and an inverse relationship between DNA density and transcription, driven by DNA condensates at the nuclear periphery devoid of newly made RNA. Collectively, these data support an evolving model of transcriptional plasticity that extends at least to a subset of chromatin at the extreme of condensation as expected of heterochromatin.","PeriodicalId":18081,"journal":{"name":"Life Science Alliance","volume":"26 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142266499","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

Crosstalk between bone metastatic cancer cells and sensory nerves in bone metastatic progression. 骨转移癌细胞与感觉神经在骨转移过程中的相互影响

IF 4.4 2区生物学

Life Science Alliance Pub Date : 2024-09-12 DOI: 10.26508/lsa.202302041

Sun H Park,Shunsuke Tsuzuki,Kelly F Contino,Jenna Ollodart,Matthew R Eber,Yang Yu,Laiton R Steele,Hiroyuki Inaba,Yuko Kamata,Takahiro Kimura,Ilsa Coleman,Peter S Nelson,Enriqueta Muñoz-Islas,Juan Miguel Jiménez-Andrade,Thomas J Martin,Kimberly D Mackenzie,Jennifer R Stratton,Fang-Chi Hsu,Christopher M Peters,Yusuke Shiozawa

{"title":"Crosstalk between bone metastatic cancer cells and sensory nerves in bone metastatic progression.","authors":"Sun H Park,Shunsuke Tsuzuki,Kelly F Contino,Jenna Ollodart,Matthew R Eber,Yang Yu,Laiton R Steele,Hiroyuki Inaba,Yuko Kamata,Takahiro Kimura,Ilsa Coleman,Peter S Nelson,Enriqueta Muñoz-Islas,Juan Miguel Jiménez-Andrade,Thomas J Martin,Kimberly D Mackenzie,Jennifer R Stratton,Fang-Chi Hsu,Christopher M Peters,Yusuke Shiozawa","doi":"10.26508/lsa.202302041","DOIUrl":"https://doi.org/10.26508/lsa.202302041","url":null,"abstract":"Although the role of peripheral nerves in cancer progression has been appreciated, little is known regarding cancer/sensory nerve crosstalk and its contribution to bone metastasis and associated pain. In this study, we revealed that the cancer/sensory nerve crosstalk plays a crucial role in bone metastatic progression. We found that (i) periosteal sensory nerves expressing calcitonin gene-related peptide (CGRP) are enriched in mice with bone metastasis; (ii) cancer patients with bone metastasis have elevated CGRP serum levels; (iii) bone metastatic patient tumor samples express elevated calcitonin receptor-like receptor (CRLR, a CGRP receptor component); (iv) higher CRLR levels in cancer patients are negatively correlated with recurrence-free survival; (v) CGRP induces cancer cell proliferation through the CRLR/p38/HSP27 pathway; and (vi) blocking sensory neuron-derived CGRP reduces cancer cell proliferation in vitro and bone metastatic progression in vivo. This suggests that CGRP-expressing sensory nerves are involved in bone metastatic progression and that the CGRP/CRLR axis may serve as a potential therapeutic target for bone metastasis.","PeriodicalId":18081,"journal":{"name":"Life Science Alliance","volume":"197 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142266500","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

Novel imaging tools to study mitochondrial morphology in Caenorhabditis elegans. 研究秀丽隐杆线粒体形态的新型成像工具。

IF 4.4 2区生物学

Life Science Alliance Pub Date : 2024-09-11 DOI: 10.26508/lsa.202402918

Miriam Valera-Alberni,Pallas Yao,Silvia Romero-Sanz,Anne Lanjuin,William B Mair

{"title":"Novel imaging tools to study mitochondrial morphology in Caenorhabditis elegans.","authors":"Miriam Valera-Alberni,Pallas Yao,Silvia Romero-Sanz,Anne Lanjuin,William B Mair","doi":"10.26508/lsa.202402918","DOIUrl":"https://doi.org/10.26508/lsa.202402918","url":null,"abstract":"Mitochondria exhibit a close interplay between their structure and function. Understanding this intricate relationship requires advanced imaging techniques that can capture the dynamic nature of mitochondria and their impact on cellular processes. However, much of the work on mitochondrial dynamics has been performed in single celled organisms or in vitro cell culture. Here, we introduce novel genetic tools for live imaging of mitochondrial morphology in the nematode Caenorhabditis elegans, addressing a pressing need for advanced techniques in studying organelle dynamics within live intact multicellular organisms. Through a comprehensive analysis, we directly compare our tools with existing methods, demonstrating their advantages for visualizing mitochondrial morphology and contrasting their impact on organismal physiology. We reveal limitations of conventional techniques, whereas showcasing the utility and versatility of our approaches, including endogenous CRISPR tags and ectopic labeling. By providing a guide for selecting the most suitable tools based on experimental goals, our work advances mitochondrial research in C. elegans and enhances the strategic integration of diverse imaging modalities for a holistic understanding of organelle dynamics in living organisms.","PeriodicalId":18081,"journal":{"name":"Life Science Alliance","volume":"42 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142222655","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

Structural roles of Ump1 and β-subunit propeptides in proteasome biogenesis. 蛋白酶体生物发生过程中 Ump1 和 β-亚基前肽的结构作用

IF 4.4 2区生物学

Life Science Alliance Pub Date : 2024-09-11 DOI: 10.26508/lsa.202402865

Eric Mark,Paula C Ramos,Fleur Kayser,Jörg Höckendorff,R Jürgen Dohmen,Petra Wendler

引用次数: 0

Reprogramming of breast tumor-associated macrophages with modulation of arginine metabolism. 通过调节精氨酸代谢对乳腺肿瘤相关巨噬细胞进行重编程。

IF 3.3 2区生物学

Life Science Alliance Pub Date : 2024-08-27 Print Date: 2024-11-01 DOI: 10.26508/lsa.202302339

Veani Fernando, Xunzhen Zheng, Vandana Sharma, Osama Sweef, Eun-Seok Choi, Saori Furuta

{"title":"Reprogramming of breast tumor-associated macrophages with modulation of arginine metabolism.","authors":"Veani Fernando, Xunzhen Zheng, Vandana Sharma, Osama Sweef, Eun-Seok Choi, Saori Furuta","doi":"10.26508/lsa.202302339","DOIUrl":"10.26508/lsa.202302339","url":null,"abstract":"HER2+ breast tumors have abundant immune-suppressive cells, including M2-type tumor-associated macrophages (TAMs). Although TAMs consist of the immune-stimulatory M1 type and immune-suppressive M2 type, the M1/M2-TAM ratio is reduced in immune-suppressive tumors, contributing to their immunotherapy refractoriness. M1- versus M2-TAM formation depends on differential arginine metabolism, where M1-TAMs convert arginine to nitric oxide (NO) and M2-TAMs convert arginine to polyamines (PAs). We hypothesize that such distinct arginine metabolism in M1- versus M2-TAMs is attributed to different availability of BH4 (NO synthase cofactor) and that its replenishment would reprogram M2-TAMs to M1-TAMs. Recently, we reported that sepiapterin (SEP), the endogenous BH4 precursor, elevates the expression of M1-TAM markers within HER2+ tumors. Here, we show that SEP restores BH4 levels in M2-like macrophages, which then redirects arginine metabolism to NO synthesis and converts M2 type to M1 type. The reprogrammed macrophages exhibit full-fledged capabilities of antigen presentation and induction of effector T cells to trigger immunogenic cell death of HER2+ cancer cells. This study substantiates the utility of SEP in the metabolic shift of the HER2+ breast tumor microenvironment as a novel immunotherapeutic strategy.","PeriodicalId":18081,"journal":{"name":"Life Science Alliance","volume":"7 11","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11350068/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142080794","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

CC2D1A causes ciliopathy, intellectual disability, heterotaxy, renal dysplasia, and abnormal CSF flow. CC2D1A会导致纤毛症、智力障碍、异位发育、肾发育不良和脑脊液流动异常。

IF 3.3 2区生物学

Life Science Alliance Pub Date : 2024-08-21 Print Date: 2024-10-01 DOI: 10.26508/lsa.202402708

Angelina Haesoo Kim, Irmak Sakin, Stephen Viviano, Gulten Tuncel, Stephanie Marie Aguilera, Gizem Goles, Lauren Jeffries, Weizhen Ji, Saquib A Lakhani, Canan Ceylan Kose, Fatma Silan, Sukru Sadik Oner, Oktay I Kaplan, Mahmut Cerkez Ergoren, Ketu Mishra-Gorur, Murat Gunel, Sebnem Ozemri Sag, Sehime G Temel, Engin Deniz

{"title":"CC2D1A causes ciliopathy, intellectual disability, heterotaxy, renal dysplasia, and abnormal CSF flow.","authors":"Angelina Haesoo Kim, Irmak Sakin, Stephen Viviano, Gulten Tuncel, Stephanie Marie Aguilera, Gizem Goles, Lauren Jeffries, Weizhen Ji, Saquib A Lakhani, Canan Ceylan Kose, Fatma Silan, Sukru Sadik Oner, Oktay I Kaplan, Mahmut Cerkez Ergoren, Ketu Mishra-Gorur, Murat Gunel, Sebnem Ozemri Sag, Sehime G Temel, Engin Deniz","doi":"10.26508/lsa.202402708","DOIUrl":"10.26508/lsa.202402708","url":null,"abstract":"Intellectual and developmental disabilities result from abnormal nervous system development. Over a 1,000 genes have been associated with intellectual and developmental disabilities, driving continued efforts toward dissecting variant functionality to enhance our understanding of the disease mechanism. This report identified two novel variants in CC2D1A in a cohort of four patients from two unrelated families. We used multiple model systems for functional analysis, including Xenopus, Drosophila, and patient-derived fibroblasts. Our experiments revealed that cc2d1a is expressed explicitly in a spectrum of ciliated tissues, including the left-right organizer, epidermis, pronephric duct, nephrostomes, and ventricular zone of the brain. In line with this expression pattern, loss of cc2d1a led to cardiac heterotaxy, cystic kidneys, and abnormal CSF circulation via defective ciliogenesis. Interestingly, when we analyzed brain development, mutant tadpoles showed abnormal CSF circulation only in the midbrain region, suggesting abnormal local CSF flow. Furthermore, our analysis of the patient-derived fibroblasts confirmed defective ciliogenesis, further supporting our observations. In summary, we revealed novel insight into the role of CC2D1A by establishing its new critical role in ciliogenesis and CSF circulation.","PeriodicalId":18081,"journal":{"name":"Life Science Alliance","volume":"7 10","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11339347/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142017958","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Gene expression and chromatin conformation of microglia in virally suppressed people with HIV. 病毒抑制型艾滋病患者小胶质细胞的基因表达和染色质构象。

IF 3.3 2区生物学

Life Science Alliance Pub Date : 2024-07-26 Print Date: 2024-10-01 DOI: 10.26508/lsa.202402736

Johannes Cm Schlachetzki, Sara Gianella, Zhengyu Ouyang, Addison J Lana, Xiaoxu Yang, Sydney O'Brien, Jean F Challacombe, Peter J Gaskill, Kelly L Jordan-Sciutto, Antoine Chaillon, David Moore, Cristian L Achim, Ronald J Ellis, Davey M Smith, Christopher K Glass

{"title":"Gene expression and chromatin conformation of microglia in virally suppressed people with HIV.","authors":"Johannes Cm Schlachetzki, Sara Gianella, Zhengyu Ouyang, Addison J Lana, Xiaoxu Yang, Sydney O'Brien, Jean F Challacombe, Peter J Gaskill, Kelly L Jordan-Sciutto, Antoine Chaillon, David Moore, Cristian L Achim, Ronald J Ellis, Davey M Smith, Christopher K Glass","doi":"10.26508/lsa.202402736","DOIUrl":"10.26508/lsa.202402736","url":null,"abstract":"The presence of HIV in sequestered reservoirs is a central impediment to a functional cure, allowing HIV to persist despite life-long antiretroviral therapy (ART), and driving a variety of comorbid conditions. Our understanding of the latent HIV reservoir in the central nervous system is incomplete, because of difficulties in accessing human central nervous system tissues. Microglia contribute to HIV reservoirs, but the molecular phenotype of HIV-infected microglia is poorly understood. We leveraged the unique \"Last Gift\" rapid autopsy program, in which people with HIV are closely followed until days or even hours before death. Microglial populations were heterogeneous regarding their gene expression profiles but showed similar chromatin accessibility landscapes. Despite ART, we detected occasional microglia containing cell-associated HIV RNA and HIV DNA integrated into open regions of the host's genome (∼0.005%). Microglia with detectable HIV RNA showed an inflammatory phenotype. These results demonstrate a distinct myeloid cell reservoir in the brains of people with HIV despite suppressive ART. Strategies for curing HIV and neurocognitive impairment will need to consider the myeloid compartment to be successful.","PeriodicalId":18081,"journal":{"name":"Life Science Alliance","volume":"7 10","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11282357/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141766476","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Reduced protein-coding transcript diversity in severe dengue emphasises the role of alternative splicing. 严重登革热病中蛋白质编码转录本多样性的降低强调了替代剪接的作用。

IF 3.3 2区生物学

Life Science Alliance Pub Date : 2024-06-03 Print Date: 2024-08-01 DOI: 10.26508/lsa.202402683

Priyanka Mehta, Chinky Shiu Chen Liu, Sristi Sinha, Ramakant Mohite, Smriti Arora, Partha Chattopadhyay, Sandeep Budhiraja, Bansidhar Tarai, Rajesh Pandey

{"title":"Reduced protein-coding transcript diversity in severe dengue emphasises the role of alternative splicing.","authors":"Priyanka Mehta, Chinky Shiu Chen Liu, Sristi Sinha, Ramakant Mohite, Smriti Arora, Partha Chattopadhyay, Sandeep Budhiraja, Bansidhar Tarai, Rajesh Pandey","doi":"10.26508/lsa.202402683","DOIUrl":"10.26508/lsa.202402683","url":null,"abstract":"Dengue fever, a neglected tropical arboviral disease, has emerged as a global health concern in the past decade. Necessitating a nuanced comprehension of the intricate dynamics of host-virus interactions influencing disease severity, we analysed transcriptomic patterns using bulk RNA-seq from 112 age- and gender-matched NS1 antigen-confirmed hospital-admitted dengue patients with varying severity. Severe cases exhibited reduced platelet count, increased lymphocytosis, and neutropenia, indicating a dysregulated immune response. Using bulk RNA-seq, our analysis revealed a minimal overlap between the differentially expressed gene and transcript isoform, with a distinct expression pattern across the disease severity. Severe patients showed enrichment in retained intron and nonsense-mediated decay transcript biotypes, suggesting altered splicing efficiency. Furthermore, an up-regulated programmed cell death, a haemolytic response, and an impaired interferon and antiviral response at the transcript level were observed. We also identified the potential involvement of the RBM39 gene among others in the innate immune response during dengue viral pathogenesis, warranting further investigation. These findings provide valuable insights into potential therapeutic targets, underscoring the importance of exploring transcriptomic landscapes between different disease sub-phenotypes in infectious diseases.","PeriodicalId":18081,"journal":{"name":"Life Science Alliance","volume":"7 8","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11147948/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141237594","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Nanobodies as novel tools to monitor the mitochondrial fission factor Drp1. 纳米抗体是监测线粒体裂变因子 Drp1 的新型工具。

IF 3.3 2区生物学

Life Science Alliance Pub Date : 2024-05-30 Print Date: 2024-08-01 DOI: 10.26508/lsa.202402608

Theresa Froehlich, Andreas Jenner, Claudia Cavarischia-Rega, Funmilayo O Fagbadebo, Yannic Lurz, Desiree I Frecot, Philipp D Kaiser, Stefan Nueske, Armin M Scholz, Erik Schäffer, Ana J Garcia-Saez, Boris Macek, Ulrich Rothbauer

{"title":"Nanobodies as novel tools to monitor the mitochondrial fission factor Drp1.","authors":"Theresa Froehlich, Andreas Jenner, Claudia Cavarischia-Rega, Funmilayo O Fagbadebo, Yannic Lurz, Desiree I Frecot, Philipp D Kaiser, Stefan Nueske, Armin M Scholz, Erik Schäffer, Ana J Garcia-Saez, Boris Macek, Ulrich Rothbauer","doi":"10.26508/lsa.202402608","DOIUrl":"10.26508/lsa.202402608","url":null,"abstract":"In cells, mitochondria undergo constant fusion and fission. An essential factor for fission is the mammalian dynamin-related protein 1 (Drp1). Dysregulation of Drp1 is associated with neurodegenerative diseases including Parkinson's, cardiovascular diseases and cancer, making Drp1 a pivotal biomarker for monitoring mitochondrial status and potential pathophysiological conditions. Here, we developed nanobodies (Nbs) as versatile binding molecules for proteomics, advanced microscopy and live cell imaging of Drp1. To specifically enrich endogenous Drp1 with interacting proteins for proteomics, we functionalized high-affinity Nbs into advanced capture matrices. Furthermore, we detected Drp1 by bivalent Nbs combined with site-directed fluorophore labelling in super-resolution STORM microscopy. For real-time imaging of Drp1, we intracellularly expressed fluorescently labelled Nbs, so-called chromobodies (Cbs). To improve the signal-to-noise ratio, we further converted Cbs into a \"turnover-accelerated\" format. With these imaging probes, we visualized the dynamics of endogenous Drp1 upon compound-induced mitochondrial fission in living cells. Considering the wide range of research applications, the presented Nb toolset will open up new possibilities for advanced functional studies of Drp1 in disease-relevant models.","PeriodicalId":18081,"journal":{"name":"Life Science Alliance","volume":"7 8","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11140114/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141180355","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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