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The promise of genetic screens in human in vitro brain models. 体外人脑模型基因筛选的前景。
IF 2.9 4区 生物学
Biological Chemistry Pub Date : 2023-09-12 Print Date: 2024-01-29 DOI: 10.1515/hsz-2023-0174
Julianne Beirute-Herrera, Beatriz López-Amo Calvo, Frank Edenhofer, Christopher Esk
{"title":"The promise of genetic screens in human <i>in vitro</i> brain models.","authors":"Julianne Beirute-Herrera, Beatriz López-Amo Calvo, Frank Edenhofer, Christopher Esk","doi":"10.1515/hsz-2023-0174","DOIUrl":"10.1515/hsz-2023-0174","url":null,"abstract":"<p><p>Advances of <i>in vitro</i> culture models have allowed unprecedented insights into human neurobiology. At the same time genetic screening has matured into a robust and accessible experimental strategy allowing for the simultaneous study of many genes in parallel. The combination of both technologies is a newly emerging tool for neuroscientists, opening the door to identifying causal cell- and tissue-specific developmental and disease mechanisms. However, with complex experimental genetic screening set-ups new challenges in data interpretation and experimental scope arise that require a deep understanding of the benefits and challenges of individual approaches. In this review, we summarize the literature that applies genetic screening to <i>in vitro</i> brain models, compare experimental strengths and weaknesses and point towards future directions of these promising approaches.</p>","PeriodicalId":8885,"journal":{"name":"Biological Chemistry","volume":" ","pages":"13-24"},"PeriodicalIF":2.9,"publicationDate":"2023-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10213932","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
N6-methyladenosine-induced METTL1 promotes tumor proliferation via CDK4. N6-甲基腺苷诱导的 METTL1 通过 CDK4 促进肿瘤增殖。
IF 2.9 4区 生物学
Biological Chemistry Pub Date : 2023-09-12 Print Date: 2024-03-25 DOI: 10.1515/hsz-2023-0260
Chunyan Zhang, Yuanbo Cui
{"title":"N6-methyladenosine-induced METTL1 promotes tumor proliferation via CDK4.","authors":"Chunyan Zhang, Yuanbo Cui","doi":"10.1515/hsz-2023-0260","DOIUrl":"10.1515/hsz-2023-0260","url":null,"abstract":"<p><p>N6-methyladenosine (m6A) and N7-methylguanosine (m7G) modification of RNA represent two major intracellular post-transcriptional regulation modes of gene expression. However, the crosstalk of these two epigenetic modifications in tumorigenesis remain poorly understood. Here, we show that m6A methyltransferase METTL3-mediated METTL1 promotes cell proliferation of head and neck squamous cell carcinoma (HNSC) through m7G modification of the cell-cycle regulator CDK4. By mining the database GEPIA, METTL1 was shown to be up-regulated in a broad spectrum of human cancers and correlated with patient clinical outcomes, particularly in HNSC. Mechanistically, METTL3 methylates METTL1 mRNA and mediates its elevation in HNSC via m6A. Functionally, over-expression of METTL1 enhances HNSC cell growth and facilitates cell-cycle progress, while METTL1 knockdown represses these biological behaviors. Moreover, METTL1 physically binds to CDK4 transcript and regulates its m7G modification level to stabilize CDK4. Importantly, the inhibitory effects of METTL1 knockdown on the proliferation of HNSC, esophageal cancer (ESCA), stomach adenocarcinoma (STAD), and colon adenocarcinoma (COAD) were significantly mitigated by over-expression of CDK4. Taken together, this study expands the understanding of epigenetic mechanisms involved in tumorigenesis and identifies the METTL1/CDK4 axis as a potential therapeutic target for digestive system tumors.</p>","PeriodicalId":8885,"journal":{"name":"Biological Chemistry","volume":" ","pages":"217-228"},"PeriodicalIF":2.9,"publicationDate":"2023-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10202840","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
Microtubules as a signal hub for axon growth in response to mechanical force. 微管作为轴突生长响应机械力的信号中枢。
IF 3.7 4区 生物学
Biological Chemistry Pub Date : 2023-09-08 Print Date: 2024-01-29 DOI: 10.1515/hsz-2023-0173
Alessandro Falconieri, Allegra Coppini, Vittoria Raffa
{"title":"Microtubules as a signal hub for axon growth in response to mechanical force.","authors":"Alessandro Falconieri, Allegra Coppini, Vittoria Raffa","doi":"10.1515/hsz-2023-0173","DOIUrl":"10.1515/hsz-2023-0173","url":null,"abstract":"<p><p>Microtubules are highly polar structures and are characterized by high anisotropy and stiffness. In neurons, they play a key role in the directional transport of vesicles and organelles. In the neuronal projections called axons, they form parallel bundles, mostly oriented with the plus-end towards the axonal termination. Their physico-chemical properties have recently attracted attention as a potential candidate in sensing, processing and transducing physical signals generated by mechanical forces. Here, we discuss the main evidence supporting the role of microtubules as a signal hub for axon growth in response to a traction force. Applying a tension to the axon appears to stabilize the microtubules, which, in turn, coordinate a modulation of axonal transport, local translation and their cross-talk. We speculate on the possible mechanisms modulating microtubule dynamics under tension, based on evidence collected in neuronal and non-neuronal cell types. However, the fundamental question of the causal relationship between these mechanisms is still elusive because the mechano-sensitive element in this chain has not yet been identified.</p>","PeriodicalId":8885,"journal":{"name":"Biological Chemistry","volume":" ","pages":"67-77"},"PeriodicalIF":3.7,"publicationDate":"2023-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10161279","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
The Zika virus infection remodels the expression of the synaptotagmin-9 secretory protein. 寨卡病毒感染重塑了突触标记蛋白-9分泌蛋白的表达。
IF 2.9 4区 生物学
Biological Chemistry Pub Date : 2023-09-08 Print Date: 2024-03-25 DOI: 10.1515/hsz-2023-0165
Santiago Leiva, Alejo Cantoia, Cintia Fabbri, Marina Bugnon Valdano, Victoria Luppo, María Alejandra Morales, Germán Rosano, Daniela Gardiol
{"title":"The Zika virus infection remodels the expression of the synaptotagmin-9 secretory protein.","authors":"Santiago Leiva, Alejo Cantoia, Cintia Fabbri, Marina Bugnon Valdano, Victoria Luppo, María Alejandra Morales, Germán Rosano, Daniela Gardiol","doi":"10.1515/hsz-2023-0165","DOIUrl":"10.1515/hsz-2023-0165","url":null,"abstract":"<p><p>The exact mechanisms involved in flaviviruses virions' release and the specific secretion of viral proteins, such as the Non Structural protein-1 (NS1), are still unclear. While these processes might involve vesicular transport to the cell membrane, NS1 from some flaviviruses was shown to participate in viral assembly and release. Here, we assessed the effect of the Zika virus (ZIKV) NS1 expression on the cellular proteome to identify trafficking-related targets that may be altered in the presence of the viral protein. We detected an increase in the synaptotagmin-9 (SYT9) secretory protein, which participates in the intracellular transport of protein-laden vesicles. We confirmed the effect of NS1 on SYT9 levels by transfection models while also detecting a significant subcellular redistribution of SYT9. We found that ZIKV prM-Env proteins, required for the viral particle release, also increased SYT9 levels and changed its localization. Finally, we demonstrated that ZIKV cellular infection raises SYT9 levels and promotes changes in its subcellular localization, together with a co-distribution with both Env and NS1. Altogether, the data suggest SYT9's implication in the vesicular transport of viral proteins or virions during ZIKV infection, showing for the first time the association of synaptotagmins with the flavivirus' life cycle.</p>","PeriodicalId":8885,"journal":{"name":"Biological Chemistry","volume":" ","pages":"189-201"},"PeriodicalIF":2.9,"publicationDate":"2023-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10180542","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
Cytosolic RGG RNA-binding proteins are temperature sensitive flowering time regulators in Arabidopsis. 拟南芥细胞质RGG rna结合蛋白是温度敏感的开花时间调节因子。
IF 3.7 4区 生物学
Biological Chemistry Pub Date : 2023-09-08 Print Date: 2023-10-26 DOI: 10.1515/hsz-2023-0171
Andrea Bleckmann, Nicole Spitzlberger, Philipp Denninger, Hans F Ehrnsberger, Lele Wang, Astrid Bruckmann, Stefan Reich, Philipp Holzinger, Jan Medenbach, Klaus D Grasser, Thomas Dresselhaus
{"title":"Cytosolic RGG RNA-binding proteins are temperature sensitive flowering time regulators in <i>Arabidopsis</i>.","authors":"Andrea Bleckmann, Nicole Spitzlberger, Philipp Denninger, Hans F Ehrnsberger, Lele Wang, Astrid Bruckmann, Stefan Reich, Philipp Holzinger, Jan Medenbach, Klaus D Grasser, Thomas Dresselhaus","doi":"10.1515/hsz-2023-0171","DOIUrl":"10.1515/hsz-2023-0171","url":null,"abstract":"<p><p>mRNA translation is tightly regulated by various classes of RNA-binding proteins (RBPs) during development and in response to changing environmental conditions. In this study, we characterize the arginine-glycine-glycine (RGG) motif containing RBP family of <i>Arabidopsis thaliana</i> representing homologues of the multifunctional translation regulators and ribosomal preservation factors Stm1 from yeast (ScStm1) and human SERBP1 (HsSERBP1). The Arabidopsis genome encodes three RGG proteins named AtRGGA, AtRGGB and AtRGGC. While AtRGGA is ubiquitously expressed, AtRGGB and AtRGGC are enriched in dividing cells. All AtRGGs localize almost exclusively to the cytoplasm and bind with high affinity to ssRNA, while being capable to interact with most nucleic acids, except dsRNA. A protein-interactome study shows that AtRGGs interact with ribosomal proteins and proteins involved in RNA processing and transport. In contrast to ScStm1, AtRGGs are enriched in ribosome-free fractions in polysome profiles, suggesting additional plant-specific functions. Mutant studies show that AtRGG proteins differentially regulate flowering time, with a distinct and complex temperature dependency for each AtRGG protein. In conclusion, we suggest that AtRGGs function in fine-tuning translation efficiency to control flowering time and potentially other developmental processes in response to environmental changes.</p>","PeriodicalId":8885,"journal":{"name":"Biological Chemistry","volume":" ","pages":"1069-1084"},"PeriodicalIF":3.7,"publicationDate":"2023-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10542281","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
Nanoscale organization of CaV2.1 splice isoforms at presynaptic terminals: implications for synaptic vesicle release and synaptic facilitation. 突触前末端CaV2.1剪接异构体的纳米级组织：对突触小泡释放和突触促进的意义。
IF 2.9 4区 生物学
Biological Chemistry Pub Date : 2023-09-04 Print Date: 2023-09-26 DOI: 10.1515/hsz-2023-0235
Lorenzo A Cingolani, Agnes Thalhammer, Fanny Jaudon, Jessica Muià, Gabriele Baj
{"title":"Nanoscale organization of Ca<sub>V</sub>2.1 splice isoforms at presynaptic terminals: implications for synaptic vesicle release and synaptic facilitation.","authors":"Lorenzo A Cingolani, Agnes Thalhammer, Fanny Jaudon, Jessica Muià, Gabriele Baj","doi":"10.1515/hsz-2023-0235","DOIUrl":"10.1515/hsz-2023-0235","url":null,"abstract":"<p><p>The distance between Ca<sub>V</sub>2.1 voltage-gated Ca<sup>2+</sup> channels and the Ca<sup>2+</sup> sensor responsible for vesicle release at presynaptic terminals is critical for determining synaptic strength. Yet, the molecular mechanisms responsible for a loose coupling configuration of Ca<sub>V</sub>2.1 in certain synapses or developmental periods and a tight one in others remain unknown. Here, we examine the nanoscale organization of two Ca<sub>V</sub>2.1 splice isoforms (Ca<sub>V</sub>2.1[EFa] and Ca<sub>V</sub>2.1[EFb]) at presynaptic terminals by superresolution structured illumination microscopy. We find that Ca<sub>V</sub>2.1[EFa] is more tightly co-localized with presynaptic markers than Ca<sub>V</sub>2.1[EFb], suggesting that alternative splicing plays a crucial role in the synaptic organization of Ca<sub>V</sub>2.1 channels.</p>","PeriodicalId":8885,"journal":{"name":"Biological Chemistry","volume":"404 10","pages":"931-937"},"PeriodicalIF":2.9,"publicationDate":"2023-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10695435/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10631489","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
The emerging role of ATP as a cosolute for biomolecular processes. ATP作为生物分子过程的共溶物的新兴作用。
IF 3.7 4区 生物学
Biological Chemistry Pub Date : 2023-09-04 Print Date: 2023-09-26 DOI: 10.1515/hsz-2023-0202
Alexander Hautke, Simon Ebbinghaus
{"title":"The emerging role of ATP as a cosolute for biomolecular processes.","authors":"Alexander Hautke,&nbsp;Simon Ebbinghaus","doi":"10.1515/hsz-2023-0202","DOIUrl":"10.1515/hsz-2023-0202","url":null,"abstract":"<p><p>ATP is an important small molecule that appears at outstandingly high concentration within the cellular medium. Apart from its use as a source of energy and a metabolite, there is increasing evidence for important functions as a cosolute for biomolecular processes. Owned to its solubilizing kosmotropic triphosphate and hydrophobic adenine moieties, ATP is a versatile cosolute that can interact with biomolecules in various ways. We here use three models to categorize these interactions and apply them to review recent studies. We focus on the impact of ATP on biomolecular solubility, folding stability and phase transitions. This leads us to possible implications and therapeutic interventions in neurodegenerative diseases.</p>","PeriodicalId":8885,"journal":{"name":"Biological Chemistry","volume":"404 10","pages":"897-908"},"PeriodicalIF":3.7,"publicationDate":"2023-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10283339","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
Highlights in biochemistry Bochum 2022. 生物化学亮点波鸿2022。
IF 2.9 4区 生物学
Biological Chemistry Pub Date : 2023-09-04 Print Date: 2023-09-26 DOI: 10.1515/hsz-2023-0276
Rolf Heumann
{"title":"Highlights in biochemistry Bochum 2022.","authors":"Rolf Heumann","doi":"10.1515/hsz-2023-0276","DOIUrl":"10.1515/hsz-2023-0276","url":null,"abstract":"","PeriodicalId":8885,"journal":{"name":"Biological Chemistry","volume":"404 10","pages":"881-882"},"PeriodicalIF":2.9,"publicationDate":"2023-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10282490","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
Frontmatter 头版头条
4区 生物学
Biological Chemistry Pub Date : 2023-09-01 DOI: 10.1515/hsz-2023-frontmatter10
{"title":"Frontmatter","authors":"","doi":"10.1515/hsz-2023-frontmatter10","DOIUrl":"https://doi.org/10.1515/hsz-2023-frontmatter10","url":null,"abstract":"","PeriodicalId":8885,"journal":{"name":"Biological Chemistry","volume":"39 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135347404","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
Optogenetics 2.0: challenges and solutions towards a quantitative probing of neural circuits. 光遗传学2.0:神经回路定量探测的挑战和解决方案。
IF 3.7 4区 生物学
Biological Chemistry Pub Date : 2023-08-31 Print Date: 2024-01-29 DOI: 10.1515/hsz-2023-0194
Saleh Altahini, Isabelle Arnoux, Albrecht Stroh
{"title":"Optogenetics 2.0: challenges and solutions towards a quantitative probing of neural circuits.","authors":"Saleh Altahini, Isabelle Arnoux, Albrecht Stroh","doi":"10.1515/hsz-2023-0194","DOIUrl":"10.1515/hsz-2023-0194","url":null,"abstract":"<p><p>To exploit the full potential of optogenetics, we need to titrate and tailor optogenetic methods to emulate naturalistic circuit function. For that, the following prerequisites need to be met: first, we need to target opsin expression not only to genetically defined neurons per se, but to specifically target a functional node. Second, we need to assess the scope of optogenetic modulation, i.e. the fraction of optogenetically modulated neurons. Third, we need to integrate optogenetic control in a closed loop setting. Fourth, we need to further safe and stable gene expression and light delivery to bring optogenetics to the clinics. Here, we review these concepts for the human and rodent brain.</p>","PeriodicalId":8885,"journal":{"name":"Biological Chemistry","volume":" ","pages":"43-54"},"PeriodicalIF":3.7,"publicationDate":"2023-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10122638","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
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