Open BiologyPub Date : 2024-05-01DOI: 10.1098/rsob.230358
Bo Fu, Hong Ma, Di Liu
{"title":"Essential roles of the nucleolus during early embryonic development: a regulatory hub for chromatin organization","authors":"Bo Fu, Hong Ma, Di Liu","doi":"10.1098/rsob.230358","DOIUrl":"https://doi.org/10.1098/rsob.230358","url":null,"abstract":"<p>The nucleolus is the most prominent liquid droplet-like membrane-less organelle in mammalian cells. Unlike the nucleolus in terminally differentiated somatic cells, those in totipotent cells, such as murine zygotes or two-cell embryos, have a unique nucleolar structure known as nucleolus precursor bodies (NPBs). Previously, it was widely accepted that NPBs in zygotes are simply passive repositories of materials that will be gradually used to construct a fully functional nucleolus after zygotic genome activation (ZGA). However, recent research studies have challenged this simplistic view and demonstrated that functions of the NPBs go beyond ribosome biogenesis. In this review, we provide a snapshot of the functions of NPBs in zygotes and early two-cell embryos in mice. We propose that these membrane-less organelles function as a regulatory hub for chromatin organization. On the one hand, NPBs provide the structural platform for centric and pericentric chromatin remodelling. On the other hand, the dynamic changes in nucleolar structure control the release of the pioneer factors (i.e. double homeobox (Dux)). It appears that during transition from totipotency to pluripotency, decline of totipotency and initiation of fully functional nucleolus formation are not independent events but are interconnected. Consequently, it is reasonable to hypothesize that dissecting more unknown functions of NPBs may shed more light on the enigmas of early embryonic development and may ultimately provide novel approaches to improve reprogramming efficiency.</p>","PeriodicalId":19629,"journal":{"name":"Open Biology","volume":"23 1","pages":""},"PeriodicalIF":5.8,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140831654","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Open BiologyPub Date : 2024-05-01Epub Date: 2024-05-29DOI: 10.1098/rsob.230430
Sverre Aarseth Tunstad, Ian D Bull, Sean A Rands, Heather M Whitney
{"title":"The cuticular wax composition and crystal coverage of leaves and petals differ in a consistent manner between plant species.","authors":"Sverre Aarseth Tunstad, Ian D Bull, Sean A Rands, Heather M Whitney","doi":"10.1098/rsob.230430","DOIUrl":"10.1098/rsob.230430","url":null,"abstract":"<p><p>Both leaves and petals are covered in a cuticle, which itself contains and is covered by cuticular waxes. The waxes perform various roles in plants' lives, and the cuticular composition of leaves has received much attention. To date, the cuticular composition of petals has been largely ignored. Being the outermost boundary between the plant and the environment, the cuticle is the first point of contact between a flower and a pollinator, yet we know little about how plant-pollinator interactions shape its chemical composition. Here, we investigate the general structure and composition of floral cuticular waxes by analysing the cuticular composition of leaves and petals of 49 plant species, representing 19 orders and 27 families. We show that the flowers of plants from across the phylogenetic range are nearly devoid of wax crystals and that the total wax load of leaves in 90% of the species is higher than that of petals. The proportion of alkanes is higher, and the chain lengths of the aliphatic compounds are shorter in petals than in leaves. We argue these differences are a result of adaptation to the different roles leaves and petals play in plant biology.</p>","PeriodicalId":19629,"journal":{"name":"Open Biology","volume":"14 5","pages":"230430"},"PeriodicalIF":4.5,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11293435/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141159943","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}
{"title":"Complement receptor 3-dependent engagement by <i>Candida glabrata</i> β-glucan modulates dendritic cells to induce regulatory T-cell expansion.","authors":"Areerat Kunanopparat, Truc Thi Huong Dinh, Pranpariya Ponpakdee, Panuwat Padungros, Warerat Kaewduangduen, Kasirapat Ariya-Anandech, Phawida Tummamunkong, Amanee Samaeng, Pannagorn Sae-Ear, Asada Leelahavanichkul, Nattiya Hirankarn, Patcharee Ritprajak","doi":"10.1098/rsob.230315","DOIUrl":"10.1098/rsob.230315","url":null,"abstract":"<p><p><i>Candida glabrata</i> is an important pathogen causing invasive infection associated with a high mortality rate. One mechanism that causes the failure of <i>Candida</i> eradication is an increase in regulatory T cells (Treg), which play a major role in immune suppression and promoting <i>Candida</i> pathogenicity. To date, how <i>C. glabrata</i> induces a Treg response remains unclear. Dendritic cells (DCs) recognition of fungi provides the fundamental signal determining the fate of the T-cell response. This study investigated the interplay between <i>C. glabrata</i> and DCs and its effect on Treg induction. We found that <i>C. glabrata</i> β-glucan was a major component that interacted with DCs and consequently mediated the Treg response. Blocking the binding of <i>C. glabrata</i> β-glucan to dectin-1 and complement receptor 3 (CR3) showed that CR3 activation in DCs was crucial for the induction of Treg. Furthermore, a ligand-receptor binding assay showed the preferential binding of <i>C. glabrata</i> β-glucan to CR3. Our data suggest that <i>C. glabrata</i> β-glucan potentially mediates the Treg response, probably through CR3-dependent activation in DCs. This study contributes new insights into immune modulation by <i>C. glabrata</i> that may lead to a better design of novel immunotherapeutic strategies for invasive <i>C. glabrata</i> infection.</p>","PeriodicalId":19629,"journal":{"name":"Open Biology","volume":"14 5","pages":"230315"},"PeriodicalIF":4.5,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11293457/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141159873","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}
Open BiologyPub Date : 2024-05-01Epub Date: 2024-05-22DOI: 10.1098/rsob.240021
Vít Dohnálek, Pavel Doležal
{"title":"Installation of LYRM proteins in early eukaryotes to regulate the metabolic capacity of the emerging mitochondrion.","authors":"Vít Dohnálek, Pavel Doležal","doi":"10.1098/rsob.240021","DOIUrl":"10.1098/rsob.240021","url":null,"abstract":"<p><p>Core mitochondrial processes such as the electron transport chain, protein translation and the formation of Fe-S clusters (ISC) are of prokaryotic origin and were present in the bacterial ancestor of mitochondria. In animal and fungal models, a family of small Leu-Tyr-Arg motif-containing proteins (LYRMs) uniformly regulates the function of mitochondrial complexes involved in these processes. The action of LYRMs is contingent upon their binding to the acylated form of acyl carrier protein (ACP). This study demonstrates that LYRMs are structurally and evolutionarily related proteins characterized by a core triplet of α-helices. Their widespread distribution across eukaryotes suggests that 12 specialized LYRMs were likely present in the last eukaryotic common ancestor to regulate the assembly and folding of the subunits that are conserved in bacteria but that lack LYRM homologues. The secondary reduction of mitochondria to anoxic environments has rendered the function of LYRMs and their interaction with acylated ACP dispensable. Consequently, these findings strongly suggest that early eukaryotes installed LYRMs in aerobic mitochondria as orchestrated switches, essential for regulating core metabolism and ATP production.</p>","PeriodicalId":19629,"journal":{"name":"Open Biology","volume":"14 5","pages":"240021"},"PeriodicalIF":4.5,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11293456/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141076480","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}
Open BiologyPub Date : 2024-05-01Epub Date: 2024-05-29DOI: 10.1098/rsob.230460
Maximilian Pfisterer, Roman Robert, Vera V Saul, Amelie Pritz, Markus Seibert, Regina Feederle, M Lienhard Schmitz
{"title":"The Aurora B-controlled PP1/RepoMan complex determines the spatial and temporal distribution of mitotic H2B S6 phosphorylation.","authors":"Maximilian Pfisterer, Roman Robert, Vera V Saul, Amelie Pritz, Markus Seibert, Regina Feederle, M Lienhard Schmitz","doi":"10.1098/rsob.230460","DOIUrl":"10.1098/rsob.230460","url":null,"abstract":"<p><p>The precise spatial and temporal control of histone phosphorylations is important for the ordered progression through the different phases of mitosis. The phosphorylation of H2B at S6 (H2B S6ph), which is crucial for chromosome segregation, reaches its maximum level during metaphase and is limited to the inner centromere. We discovered that the temporal and spatial regulation of this modification, as well as its intensity, are governed by the scaffold protein RepoMan and its associated catalytically active phosphatases, PP1α and PP1γ. Phosphatase activity is inhibited at the area of maximal H2B S6 phosphorylation at the inner centromere by site-specific Aurora B-mediated inactivation of the PP1/RepoMan complex. The motor protein Mklp2 contributes to the relocalization of Aurora B from chromatin to the mitotic spindle during anaphase, thus alleviating Aurora B-dependent repression of the PP1/RepoMan complex and enabling dephosphorylation of H2B S6. Accordingly, dysregulation of Mklp2 levels, as commonly observed in tumour cells, leads to the lack of H2B S6 dephosphorylation during early anaphase, which might contribute to chromosomal instability.</p>","PeriodicalId":19629,"journal":{"name":"Open Biology","volume":"14 5","pages":"230460"},"PeriodicalIF":4.5,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11293436/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141159941","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}
Open BiologyPub Date : 2024-04-17DOI: 10.1098/rsob.230383
Stefka Mincheva-Tasheva, Chandran Pfitzner, Raman Kumar, Idha Kurtsdotter, Michaela Scherer, Tarin Ritchie, Jonas Muhr, Jozef Gecz, Paul Q. Thomas
{"title":"Mapping combinatorial expression of non-clustered protocadherins in the developing brain identifies novel PCDH19-mediated cell adhesion properties","authors":"Stefka Mincheva-Tasheva, Chandran Pfitzner, Raman Kumar, Idha Kurtsdotter, Michaela Scherer, Tarin Ritchie, Jonas Muhr, Jozef Gecz, Paul Q. Thomas","doi":"10.1098/rsob.230383","DOIUrl":"https://doi.org/10.1098/rsob.230383","url":null,"abstract":"<p>Non-clustered protocadherins (ncPcdhs) are adhesive molecules with spatio-temporally regulated overlapping expression in the developing nervous system. Although their unique role in neurogenesis has been widely studied, their combinatorial role in brain physiology and pathology is poorly understood. Using probabilistic cell typing by <i>in situ</i> sequencing, we demonstrate combinatorial inter- and intra-familial expression of ncPcdhs in the developing mouse cortex and hippocampus, at single-cell resolution. We discovered the combinatorial expression of Protocadherin-19 (<i>Pcdh19</i>), a protein involved in PCDH19-clustering epilepsy, with <i>Pcdh1</i>, <i>Pcdh9</i> or Cadherin 13 (<i>Cdh13</i>) in excitatory neurons. Using aggregation assays, we demonstrate a code-specific adhesion function of PCDH19; mosaic PCDH19 absence in PCDH19+9 and PCDH19 + CDH13, but not in PCDH19+1 codes, alters cell–cell interaction. Interestingly, we found that PCDH19 as a dominant protein in two heterophilic adhesion codes could promote <i>trans</i>-interaction between them. In addition, we discovered increased CDH13-mediated cell adhesion in the presence of PCDH19, suggesting a potential role of PCDH19 as an adhesion mediator of CDH13. Finally, we demonstrated novel <i>cis</i>-interactions between PCDH19 and PCDH1, PCDH9 and CDH13. These observations suggest that there is a unique combinatorial code with a cell- and region-specific characteristic where a single molecule defines the heterophilic cell–cell adhesion properties of each code.</p>","PeriodicalId":19629,"journal":{"name":"Open Biology","volume":"301 1","pages":""},"PeriodicalIF":5.8,"publicationDate":"2024-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140608858","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Regional random mutagenesis driven by multiple sgRNAs and diverse on-target genome editing events to identify functionally important elements in non-coding regions","authors":"Kento Morimoto, Hayate Suzuki, Akihiro Kuno, Yoko Daitoku, Yoko Tanimoto, Kanako Kato, Kazuya Murata, Fumihiro Sugiyama, Seiya Mizuno","doi":"10.1098/rsob.240007","DOIUrl":"https://doi.org/10.1098/rsob.240007","url":null,"abstract":"<p>Functional regions that regulate biological phenomena are interspersed throughout eukaryotic genomes. The most definitive approach for identifying such regions is to confirm the phenotype of cells or organisms in which specific regions have been mutated or removed from the genome. This approach is invaluable for the functional analysis of genes with a defined functional element, the protein-coding sequence. By contrast, no functional analysis platforms have been established for the study of <i>cis</i>-elements or microRNA cluster regions consisting of multiple microRNAs with functional overlap. Whole-genome mutagenesis approaches, such as via <i>N</i>-ethyl-<i>N</i>-nitrosourea and gene trapping, have greatly contributed to elucidating the function of coding genes. These methods almost never induce deletions of genomic regions or multiple mutations within a narrow region. In other words, <i>cis</i>-elements and microRNA clusters cannot be effectively targeted in such a manner. Herein, we established a novel region-specific random mutagenesis method named CRISPR- and transposase-based regional mutagenesis (CTRL-mutagenesis). We demonstrate that CTRL-mutagenesis randomly induces diverse mutations within target regions in murine embryonic stem cells. Comparative analysis of mutants harbouring subtly different mutations within the same region would facilitate the further study of <i>cis</i>-element and microRNA clusters.</p>","PeriodicalId":19629,"journal":{"name":"Open Biology","volume":"40 1","pages":""},"PeriodicalIF":5.8,"publicationDate":"2024-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140590726","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Open BiologyPub Date : 2024-03-20DOI: 10.1098/rsob.230376
Selena G. Burgess, Nikki R. Paul, Mark W. Richards, James R. Ault, Laurie Askenatzis, Sophie G. Claydon, Ryan Corbyn, Laura M. Machesky, Richard Bayliss
{"title":"A nanobody inhibitor of Fascin-1 actin-bundling activity and filopodia formation","authors":"Selena G. Burgess, Nikki R. Paul, Mark W. Richards, James R. Ault, Laurie Askenatzis, Sophie G. Claydon, Ryan Corbyn, Laura M. Machesky, Richard Bayliss","doi":"10.1098/rsob.230376","DOIUrl":"https://doi.org/10.1098/rsob.230376","url":null,"abstract":"<p>Fascin-1-mediated actin-bundling activity is central to the generation of plasma membrane protrusions required for cell migration. Dysregulated formation of cellular protrusions is observed in metastatic cancers, where they are required for increased invasiveness, and is often correlated with increased Fascin-1 abundance. Therefore, there is interest in generating therapeutic Fascin-1 inhibitors. We present the identification of Nb 3E11, a nanobody inhibitor of Fascin-1 actin-bundling activity and filopodia formation. The crystal structure of the Fascin-1/Nb 3E11 complex reveals the structural mechanism of inhibition. Nb 3E11 occludes an actin-binding site on the third β-trefoil domain of Fascin-1 that is currently not targeted by chemical inhibitors. Binding of Nb 3E11 to Fascin-1 induces a conformational change in the adjacent domains to stabilize Fascin-1 in an inhibitory state similar to that adopted in the presence of small-molecule inhibitors. Nb 3E11 could be used as a tool inhibitor molecule to aid in the development of Fascin-1 targeted therapeutics.</p>","PeriodicalId":19629,"journal":{"name":"Open Biology","volume":"43 1","pages":""},"PeriodicalIF":5.8,"publicationDate":"2024-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140170528","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Open BiologyPub Date : 2024-03-01Epub Date: 2024-03-13DOI: 10.1098/rsob.230270
Evgeniya Tikhonova, Anastasia Revel-Muroz, Pavel Georgiev, Oksana Maksimenko
{"title":"Interaction of MLE with CLAMP zinc finger is involved in proper MSL proteins binding to chromosomes in <i>Drosophila</i>.","authors":"Evgeniya Tikhonova, Anastasia Revel-Muroz, Pavel Georgiev, Oksana Maksimenko","doi":"10.1098/rsob.230270","DOIUrl":"10.1098/rsob.230270","url":null,"abstract":"<p><p>The <i>Drosophila</i> male-specific lethal (MSL) complex binds to the male X chromosome to activate transcription. It comprises five proteins (MSL1, MSL2, MSL3, male absent on the first (MOF), and maleless (MLE)) and two long noncoding RNAs (lncRNAs; roX1 and roX2). The MLE helicase remodels the roX lncRNAs, enabling the lncRNA-mediated assembly of the <i>Drosophila</i> dosage compensation complex. MSL2 is expressed only in males and interacts with the N-terminal zinc finger of the transcription factor chromatin-linked adapter for MSL proteins (CLAMP), which is important for the specific recruitment of the MSL complex to the male X chromosome. Here, we found that MLE's unstructured C-terminal region interacts with the sixth zinc-finger domain of CLAMP. <i>In vitro</i>, 4-5 zinc fingers are critical for the specific DNA-binding of CLAMP with GA repeats, which constitute the core motif at the high affinity binding sites for MSL proteins. Deleting the CLAMP binding region in MLE decreases the association of MSL proteins with the male X chromosome and increases male lethality. These results suggest that interactions of unstructured regions in MSL2 and MLE with CLAMP zinc finger domains are important for the specific recruitment of the MSL complex to the male X chromosome.</p>","PeriodicalId":19629,"journal":{"name":"Open Biology","volume":"14 3","pages":"230270"},"PeriodicalIF":5.8,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10932696/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140111136","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}