Open Biology最新文献_第10页

Cebpa is required for haematopoietic stem and progenitor cell generation and maintenance in zebrafish. 斑马鱼造血干细胞和祖细胞的生成和维持需要 Cebpa。

IF 4.5 3区生物学

Open Biology Pub Date : 2024-11-01 Epub Date: 2024-11-06 DOI: 10.1098/rsob.240215

Kemin Chen, Jieyi Wu, Yuxian Zhang, Wei Liu, Xiaohui Chen, Wenqing Zhang, Zhibin Huang

{"title":"Cebpa is required for haematopoietic stem and progenitor cell generation and maintenance in zebrafish.","authors":"Kemin Chen, Jieyi Wu, Yuxian Zhang, Wei Liu, Xiaohui Chen, Wenqing Zhang, Zhibin Huang","doi":"10.1098/rsob.240215","DOIUrl":"10.1098/rsob.240215","url":null,"abstract":"The CCAAT enhancer binding protein alpha (CEBPA) is crucial for myeloid differentiation and the balance of haematopoietic stem and progenitor cell (HSPC) quiescence and self-renewal, and its dysfunction can drive leukemogenesis. However, its role in HSPC generation has not been fully elucidated. Here, we utilized various zebrafish cebpa mutants to investigate the function of Cebpa in the HSPC compartment. Co-localization analysis showed that cebpa expression is enriched in nascent HSPCs. Complete loss of Cebpa function resulted in a significant reduction in early HSPC generation and the overall HSPC pool during embryonic haematopoiesis. Interestingly, while myeloid differentiation was impaired in cebpa N-terminal mutants expressing the truncated zP30 protein, the number of HSPCs was not affected, indicating a redundant role of Cebpa P42 and P30 isoforms in HSPC development. Additionally, epistasis experiments confirmed that Cebpa functions downstream of Runx1 to regulate HSPC emergence. Our findings uncover a novel role of Cebpa isoforms in HSPC generation and maintenance, and provide new insights into HSPC development.","PeriodicalId":19629,"journal":{"name":"Open Biology","volume":"14 11","pages":"240215"},"PeriodicalIF":4.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11537755/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142583963","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Linking planar polarity signalling to actomyosin contractility during vertebrate neurulation. 将脊椎动物神经形成过程中的平面极性信号与肌动蛋白收缩性联系起来

IF 4.5 3区生物学

Open Biology Pub Date : 2024-11-01 Epub Date: 2024-11-20 DOI: 10.1098/rsob.240251

Sarka Novotna, Lorena Agostini Maia, Katarzyna Anna Radaszkiewicz, Pavel Roudnicky, Jakub Harnos

{"title":"Linking planar polarity signalling to actomyosin contractility during vertebrate neurulation.","authors":"Sarka Novotna, Lorena Agostini Maia, Katarzyna Anna Radaszkiewicz, Pavel Roudnicky, Jakub Harnos","doi":"10.1098/rsob.240251","DOIUrl":"10.1098/rsob.240251","url":null,"abstract":"Actomyosin contractility represents an ancient feature of eukaryotic cells participating in many developmental and homeostasis events, including tissue morphogenesis, muscle contraction and cell migration, with dysregulation implicated in various pathological conditions, such as cancer. At the molecular level, actomyosin comprises actin bundles and myosin motor proteins that are sensitive to posttranslational modifications like phosphorylation. While the molecular components of actomyosin are well understood, the coordination of contractility by extracellular and intracellular signals, particularly from cellular signalling pathways, remains incompletely elucidated. This study focuses on WNT/planar cell polarity (PCP) signalling, previously associated with actomyosin contractility during vertebrate neurulation. Our investigation reveals that the main cytoplasmic PCP proteins, Prickle and Dishevelled, interact with key actomyosin components such as myosin light chain 9 (MLC9), leading to its phosphorylation and localized activation. Using proteomics and microscopy approaches, we demonstrate that both PCP proteins actively control actomyosin contractility through Rap1 small GTPases in relevant in vitro and in vivo models. These findings unveil a novel mechanism of how PCP signalling regulates actomyosin contractility through MLC9 and Rap1 that is relevant to vertebrate neurulation.","PeriodicalId":19629,"journal":{"name":"Open Biology","volume":"14 11","pages":"240251"},"PeriodicalIF":4.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11576107/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142676241","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Learning-induced remodelling of inhibitory synapses in the motor cortex. 学习诱导的运动皮层抑制性突触重塑

IF 4.5 3区生物学

Open Biology Pub Date : 2024-11-01 Epub Date: 2024-11-13 DOI: 10.1098/rsob.240109

Nishita Bhembre, Annalisa Paolino, Sooraj S Das, Sumasri Guntupalli, Laura R Fenlon, Victor Anggono

{"title":"Learning-induced remodelling of inhibitory synapses in the motor cortex.","authors":"Nishita Bhembre, Annalisa Paolino, Sooraj S Das, Sumasri Guntupalli, Laura R Fenlon, Victor Anggono","doi":"10.1098/rsob.240109","DOIUrl":"10.1098/rsob.240109","url":null,"abstract":"Robust structural and functional plasticity occurs at excitatory synapses in the motor cortex in response to learning. It is well established that local spinogenesis and the subsequent maintenance of newly formed spines are crucial for motor learning. However, despite local synaptic inhibition being essential for shaping excitatory synaptic input, less is known about the structural rearrangement of inhibitory synapses following learning. In this study, we co-expressed the structural marker tdTomato and a mEmerald-tagged intrabody against gephyrin to visualize inhibitory synapses in layer 2/3 cortical neurons of wild-type CD1 mice. We found that a 1-day accelerated rotarod paradigm induced robust motor learning in male and female adult CD1 mice. Histological analyses revealed a significant increase in the surface area of gephyrin puncta in neurons within the motor cortex but not in the somatosensory cortex upon motor learning. Furthermore, this learning-induced reorganization of inhibitory synapses only occurred in dendritic shafts and not in the spines. These data suggest that learning induces experience-dependent remodelling of existing inhibitory synapses to fine-tune intrinsic plasticity and input-specific modulation of excitatory connections in the motor cortex.","PeriodicalId":19629,"journal":{"name":"Open Biology","volume":"14 11","pages":"240109"},"PeriodicalIF":4.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11557243/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142623536","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Pck2 association with the plasma membrane and efficient response of the cell integrity pathway require regulation of PI4P homeostasis by exomer. Pck2 与质膜的结合以及细胞完整性途径的高效响应需要外显子对 PI4P 平衡的调节。

IF 4.5 3区生物学

Open Biology Pub Date : 2024-11-01 Epub Date: 2024-11-13 DOI: 10.1098/rsob.240101

Esteban Moscoso-Romero, Sandra Moro, Alicia Duque, Francisco Yanguas, M-Henar Valdivieso

{"title":"Pck2 association with the plasma membrane and efficient response of the cell integrity pathway require regulation of PI4P homeostasis by exomer.","authors":"Esteban Moscoso-Romero, Sandra Moro, Alicia Duque, Francisco Yanguas, M-Henar Valdivieso","doi":"10.1098/rsob.240101","DOIUrl":"10.1098/rsob.240101","url":null,"abstract":"Exomer is a protein complex that facilitates trafficking between the Golgi and the plasma membrane (PM). Schizosaccharomyces pombe exomer is composed of Cfr1 and Bch1, and we have found that full activation of the cell integrity pathway (CIP) in response to osmotic stress requires exomer. In the wild-type, the CIP activators Rgf1 (Rho1 GEF) and Pck2 (PKC homologue) and the MEK kinase Mkh1 localize in the PM, internalize after osmotic shock and re-localize after adaptation. This re-localization is inefficient in exomer mutants. Overexpression of the PM-associated 1-phosphatidylinositol 4-kinase stt4+, and deletion of the nem1+ phosphatase suppress the defects in Pck2 dynamics in exomer mutants, but not their defect in CIP activation, demonstrating that exomer regulates CIP in additional ways. Exomer mutants accumulate PI4P in the TGN, and increasing the expression of the Golgi-associated 1-phosphatidylinositol 4-kinase pik1+ suppresses their defect in Pck2 dynamics. These findings suggest that efficient PI4P transport from the Golgi to the PM requires exomer. Mutants lacking clathrin adaptors are defective in CIP activation, but not in Pck2 dynamics or in PI4P accumulation in the Golgi. Hence, traffic from the Golgi regulates CIP activation, and exomer participates in this regulation through an exclusive mechanism.","PeriodicalId":19629,"journal":{"name":"Open Biology","volume":"14 11","pages":"240101"},"PeriodicalIF":4.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11561738/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142623669","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

SID-2 is a conserved extracellular vesicle protein that is not associated with environmental RNAi in parasitic nematodes. SID-2 是一种保守的细胞外囊泡蛋白，与寄生线虫的环境 RNAi 无关。

IF 4.5 3区生物学

Open Biology Pub Date : 2024-11-01 Epub Date: 2024-11-06 DOI: 10.1098/rsob.240190

Frances Blow, Kate Jeffrey, Franklin Wang-Ngai Chow, Inna A Nikonorova, Maureen M Barr, Atlanta G Cook, Bram Prevo, Dhanya K Cheerambathur, Amy H Buck

{"title":"SID-2 is a conserved extracellular vesicle protein that is not associated with environmental RNAi in parasitic nematodes.","authors":"Frances Blow, Kate Jeffrey, Franklin Wang-Ngai Chow, Inna A Nikonorova, Maureen M Barr, Atlanta G Cook, Bram Prevo, Dhanya K Cheerambathur, Amy H Buck","doi":"10.1098/rsob.240190","DOIUrl":"10.1098/rsob.240190","url":null,"abstract":"In the free-living nematode Caenorhabditis elegans, the transmembrane protein SID-2 imports double-stranded RNA into intestinal cells to trigger systemic RNA interference (RNAi), allowing organisms to sense and respond to environmental cues such as the presence of pathogens. This process, known as environmental RNAi, has not been observed in the most closely related parasites that are also within clade V. Previous sequence-based searches failed to identify sid-2 orthologues in available clade V parasite genomes. In this study, we identified sid-2 orthologues in these parasites using genome synteny and protein structure-based comparison, following identification of a SID-2 orthologue in extracellular vesicles from the murine intestinal parasitic nematode Heligmosomoides bakeri. Expression of GFP-tagged H. bakeri SID-2 in C. elegans showed similar localization to the intestinal apical membrane as seen for GFP-tagged C. elegans SID-2, and further showed mobility in intestinal cells in vesicle-like structures. We tested the capacity of H. bakeri SID-2 to functionally complement environmental RNAi in a C. elegans SID-2 null mutant and show that H. bakeri SID-2 does not rescue the phenotype in this context. Our work identifies SID-2 as a highly abundant EV protein whose ancestral function may be unrelated to environmental RNAi, and rather highlights an association with extracellular vesicles in nematodes.","PeriodicalId":19629,"journal":{"name":"Open Biology","volume":"14 11","pages":"240190"},"PeriodicalIF":4.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11538922/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142583965","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Ultrastructural features of psychological stress resilience in the brain: a microglial perspective. 大脑心理压力复原力的超微结构特征：小胶质细胞视角。

IF 4.5 3区生物学

Open Biology Pub Date : 2024-11-01 Epub Date: 2024-11-20 DOI: 10.1098/rsob.240079

Fernando González Ibáñez, Jared VanderZwaag, Jessica Deslauriers, Marie-Ève Tremblay

{"title":"Ultrastructural features of psychological stress resilience in the brain: a microglial perspective.","authors":"Fernando González Ibáñez, Jared VanderZwaag, Jessica Deslauriers, Marie-Ève Tremblay","doi":"10.1098/rsob.240079","DOIUrl":"10.1098/rsob.240079","url":null,"abstract":"Psychological stress is the major risk factor for major depressive disorder. Sustained stress causes changes in behaviour, brain connectivity and in its cells and organelles. Resilience to stress is understood as the ability to recover from stress in a positive way or the resistance to the negative effects of psychological stress. Microglia, the resident immune cells of the brain, are known players of stress susceptibility, but less is known about their role in stress resilience and the cellular changes involved. Ultrastructural analysis has been a useful tool in the study of microglia and their function across contexts of health and disease. Despite increased access to electron microscopy, the interpretation of electron micrographs remains much less accessible. In this review, we will first present microglia and the concepts of psychological stress susceptibility and resilience. Afterwards, we will describe ultrastructural analysis, notably of microglia, as a readout to study the mechanisms underlying psychological stress resilience. Lastly, we will cover nutritional ketosis as a therapeutic intervention that was shown to be effective in promoting psychological stress resilience as well as modifying microglial function and ultrastructure.","PeriodicalId":19629,"journal":{"name":"Open Biology","volume":"14 11","pages":"240079"},"PeriodicalIF":4.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11576122/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142676250","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

An endoplasmic reticulum localized acetyl-CoA transporter is required for efficient fatty acid synthesis in Toxoplasma gondii. 弓形虫体内脂肪酸的高效合成需要内质网定位的乙酰-CoA 转运体。

IF 4.5 3区生物学

Open Biology Pub Date : 2024-11-01 Epub Date: 2024-11-13 DOI: 10.1098/rsob.240184

Biyun Qin, Bolin Fan, Yazhou Li, Yidan Wang, Bang Shen, Ningbo Xia

{"title":"An endoplasmic reticulum localized acetyl-CoA transporter is required for efficient fatty acid synthesis in Toxoplasma gondii.","authors":"Biyun Qin, Bolin Fan, Yazhou Li, Yidan Wang, Bang Shen, Ningbo Xia","doi":"10.1098/rsob.240184","DOIUrl":"10.1098/rsob.240184","url":null,"abstract":"Toxoplasma gondii is an obligate intracellular parasite that can infect humans and diverse animals. Fatty acids are critical for the growth and proliferation of T. gondii, which has at least two pathways to synthesize fatty acids, including the type II de novo synthesis pathway in the apicoplast and the elongation pathway in the endoplasmic reticulum (ER). Acetyl-CoA is the key substrate for both fatty acid synthesis pathways. In the apicoplast, acetyl-CoA is mainly provided by the pyruvate dehydrogenase complex. However, how the ER acquires acetyl-CoA is not fully understood. Here, we identified a putative acetyl-CoA transporter (TgAT1) that localized to the ER of T. gondii. Deletion of TgAT1 impaired parasite growth and invasion in vitro and attenuated tachyzoite virulence in vivo. Metabolic tracing using 13C-acetate found that loss of TgAT1 reduced the incorporation of 13C into certain fatty acids, suggesting reduced activities of elongation. Truncation of AT1 was previously reported to confer resistance to the antimalarial compound GNF179 in Plasmodium falciparum. Interestingly, GNF179 had much weaker inhibitory effect on Toxoplasma than on Plasmodium. In addition, deletion of AT1 did not affect the susceptibility of Toxoplasma to GNF179, suggesting that this compound might be taken up differently or has different inhibitory mechanisms in these parasites. Together, our data show that TgAT1 has important roles for parasite growth and fatty acid synthesis, but its disruption does not confer GNF179 resistance in T. gondii.","PeriodicalId":19629,"journal":{"name":"Open Biology","volume":"14 11","pages":"240184"},"PeriodicalIF":4.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11557232/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142625345","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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 structure of an amyloid precursor protein/talin complex indicates a mechanical basis of Alzheimer's disease. 淀粉样前体蛋白/泰林复合物的结构表明了阿尔茨海默病的机械基础。

IF 4.5 3区生物学

Open Biology Pub Date : 2024-11-01 Epub Date: 2024-11-27 DOI: 10.1098/rsob.240185

Charles Ellis, Natasha L Ward, Matthew Rice, Neil J Ball, Pauline Walle, Chloé Najdek, Devrim Kilinc, Jean-Charles Lambert, Julien Chapuis, Benjamin T Goult

{"title":"The structure of an amyloid precursor protein/talin complex indicates a mechanical basis of Alzheimer's disease.","authors":"Charles Ellis, Natasha L Ward, Matthew Rice, Neil J Ball, Pauline Walle, Chloé Najdek, Devrim Kilinc, Jean-Charles Lambert, Julien Chapuis, Benjamin T Goult","doi":"10.1098/rsob.240185","DOIUrl":"10.1098/rsob.240185","url":null,"abstract":"Misprocessing of amyloid precursor protein (APP) is one of the major causes of Alzheimer's disease. APP comprises a large extracellular region, a single transmembrane helix and a short cytoplasmic tail containing an NPxY motif (normally referred to as the YENPTY motif). Talins are synaptic scaffold proteins that connect the cytoskeletal machinery to the plasma membrane via binding NPxY motifs in the cytoplasmic tail of integrins. Here, we report the crystal structure of an APP/talin1 complex identifying a new way to couple the cytoskeletal machinery to synaptic sites through APP. Proximity ligation assay (PLA) confirmed the close proximity of talin1 and APP in primary neurons, and talin1 depletion had a dramatic effect on APP processing in cells. Structural modelling reveals APP might form an extracellular meshwork that mechanically couples the cytoskeletons of the pre- and post-synaptic compartments. We propose APP processing represents a mechanical signalling pathway whereby under tension, the cleavage sites in APP have varying accessibility to cleavage by secretases. This leads us to propose a new hypothesis for Alzheimer's, where misregulated APP dynamics result in loss of the mechanical integrity of the synapse, corruption and loss of mechanical binary data, and excessive generation of toxic plaque-forming Aβ42 peptide.","PeriodicalId":19629,"journal":{"name":"Open Biology","volume":"14 11","pages":"240185"},"PeriodicalIF":4.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11597407/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142731038","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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 pivotal role of osteopontin in UV-induced skin inflammation in a mouse model. 在小鼠模型中，骨素在紫外线诱发的皮肤炎症中发挥了关键作用。

IF 4.5 3区生物学

Open Biology Pub Date : 2024-11-01 Epub Date: 2024-11-13 DOI: 10.1098/rsob.230397

Haesoo Kim, Chang-Yup Shin, Chi-Hyun Park, Dong Hun Lee, Si-Hyung Lee, Jin Ho Chung

{"title":"The pivotal role of osteopontin in UV-induced skin inflammation in a mouse model.","authors":"Haesoo Kim, Chang-Yup Shin, Chi-Hyun Park, Dong Hun Lee, Si-Hyung Lee, Jin Ho Chung","doi":"10.1098/rsob.230397","DOIUrl":"10.1098/rsob.230397","url":null,"abstract":"Osteopontin (OPN) is a pro-inflammatory protein that influences bone remodelling, wound healing, angiogenesis, allergic inflammation, and skin diseases such as psoriasis, contact dermatitis and skin cancer. However, the role of OPN in the skin remains unclear. Therefore, this study aimed to investigate the role of OPN in the skin, particularly in the context of ultraviolet (UV) irradiation-induced inflammation. OPN expression and its effects on inflammatory modulators were assessed in human skin, in a mouse model and in vitro, using a UV source emitting both UVB and UVA radiation, which collectively contribute to UV-induced skin inflammation. OPN expression increased in human and mouse skin after UV irradiation. Compared with wild-type mice, UV irradiation-induced skin phenotypes, such as erythema and skin thickening, were alleviated in OPN-/- mice. In addition, the number of immune cells recruited to the skin after UV irradiation and the expression of inflammatory cytokines and matrix metalloproteinases (MMPs) were observed to be decreased in the skin of OPN-/- mice compared with that of wild-type mice. By contrast, the degree of skin inflammation was higher in the hOPN KI mice than in wild-type mice. Treatment with recombinant OPN increased the expression of MMP-1 and inflammatory cytokines in human dermal fibroblasts and epidermal keratinocytes in vitro. Our results suggest that OPN may play a regulatory role in UV-induced skin inflammation.","PeriodicalId":19629,"journal":{"name":"Open Biology","volume":"14 11","pages":"230397"},"PeriodicalIF":4.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11558241/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142624322","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Moesin contributes to heat shock gene response through direct binding to the Med15 subunit of the Mediator complex in the nucleus. Moesin 通过与细胞核中 Mediator 复合物的 Med15 亚基直接结合，促进热休克基因的反应。

IF 4.5 3区生物学

Open Biology Pub Date : 2024-10-01 Epub Date: 2024-10-02 DOI: 10.1098/rsob.240110

Ildikó Kristó, Zoltán Kovács, Anikó Szabó, Péter Borkúti, Alexandra Gráf, Ádám Tamás Sánta, Aladár Pettkó-Szandtner, Edit Ábrahám, Viktor Honti, Zoltán Lipinszki, Péter Vilmos

{"title":"Moesin contributes to heat shock gene response through direct binding to the Med15 subunit of the Mediator complex in the nucleus.","authors":"Ildikó Kristó, Zoltán Kovács, Anikó Szabó, Péter Borkúti, Alexandra Gráf, Ádám Tamás Sánta, Aladár Pettkó-Szandtner, Edit Ábrahám, Viktor Honti, Zoltán Lipinszki, Péter Vilmos","doi":"10.1098/rsob.240110","DOIUrl":"10.1098/rsob.240110","url":null,"abstract":"The members of the evolutionary conserved actin-binding Ezrin, Radixin and Moesin (ERM) protein family are involved in numerous key cellular processes in the cytoplasm. In the last decades, ERM proteins, like actin and other cytoskeletal components, have also been shown to be functional components of the nucleus; however, the molecular mechanism behind their nuclear activities remained unclear. Therefore, our primary aim was to identify the nuclear protein interactome of the single Drosophila ERM protein, Moesin. We demonstrate that Moesin directly interacts with the Mediator complex through direct binding to its Med15 subunit, and the presence of Moesin at the regulatory regions of the Hsp70Ab heat shock gene was found to be Med15-dependent. Both Moesin and Med15 bind to heat shock factor (Hsf), and they are required for proper Hsp gene expression under physiological conditions. Moreover, we confirmed that Moesin, Med15 and Hsf are able to bind the monomeric form of actin and together they form a complex in the nucleus. These results elucidate a mechanism by which ERMs function within the nucleus. Finally, we present the direct interaction of the human orthologues of Drosophila Moesin and Med15, which highlights the evolutionary significance of our finding.","PeriodicalId":19629,"journal":{"name":"Open Biology","volume":"14 10","pages":"240110"},"PeriodicalIF":4.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11444770/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142366072","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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