Microscopic Visualization of Cell-Cell Adhesion Complexes at Micro and Nanoscale DOI Creative Commons
Bieke Vanslembrouck, Jian-Hua Chen, Carolyn A. Larabell

et al.

Frontiers in Cell and Developmental Biology, Journal Year: 2022, Volume and Issue: 10

Published: April 20, 2022

Considerable progress has been made in our knowledge of the morphological and functional varieties anchoring junctions. Cell-cell adhesion contacts consist discrete junctional structures responsible for mechanical coupling cytoskeletons allow transmission signals across cell collective. The three main complexes are adherens junctions, tight desmosomes. Microscopy played a fundamental role understanding these on different levels both physiological pathological conditions. In this review, we discuss light electron microscopy techniques used to unravel structure composition cell-cell epithelial endothelial cells. It functions as guide pick appropriate imaging technique(s) interest. We also point out latest that have emerged. At end, problems investigators encounter during their research using microscopic techniques.

Language: Английский

The Mediator complex as a master regulator of transcription by RNA polymerase II DOI Open Access
William F. Richter, Shraddha Nayak, Janet Iwasa

et al.

Nature Reviews Molecular Cell Biology, Journal Year: 2022, Volume and Issue: 23(11), P. 732 - 749

Published: June 20, 2022

Language: Английский

Citations

198
Technological advances in super-resolution microscopy to study cellular processes DOI Creative Commons
Charles Bond, Adriana N. Santiago-Ruiz, Qing Tang

et al.

Molecular Cell, Journal Year: 2022, Volume and Issue: 82(2), P. 315 - 332

Published: Jan. 1, 2022

Language: Английский

Citations

80
The Mediator kinase module: an interface between cell signaling and transcription DOI Creative Commons
Olivia Luyties, Dylan J. Taatjes

Trends in Biochemical Sciences, Journal Year: 2022, Volume and Issue: 47(4), P. 314 - 327

Published: Feb. 19, 2022

The Mediator kinase module transforms function through physical interaction and its activity.The regulates transcription by altering factor at enhancers promoters.Rapid, stimulus-specific transcriptional responses are enabled the module.By controlling (TF) polymerase II (pol II) activity, helps convert signaling inputs to outputs. complex controls RNA activity coordinating assembly of pol regulatory factors start sites mediating interactions between enhancer-bound (TFs) enzyme. structure is completely altered upon binding module, a multi-subunit that contains CDK8 or vertebrate-specific paralog CDK19. Here, we review mechanisms which transcription, emphasizing impact on TF elongation, enhancer function, chromatin architecture. We also highlight how integrates pathways with enable rapid, responses, as well links human disease. (see Glossary) genome-wide regulator transcription; consequently, itself targeted an array regulate function. For example, sequence-specific, DNA-binding TFs bind control recruitment specific genomic loci. Also, reversibly associates (forming what here call CDK-Mediator) in several ways. Conserved from yeast humans, consists four subunits: kinase, CCNC, MED12, MED13. However, vertebrates evolved subunit paralogs, called CDK19, MED12L, MED13L (Box 1), expand functional diversity ways remain poorly defined. Not surprisingly, subunits required for mammalian embryogenesis [1.Li N. et al.Cyclin C haploinsufficient tumour suppressor.Nat. Cell Biol. 2014; 16: 1080-1091Google Scholar, 2.Miao Y.L. al.Mediator component MED13 zygotic genome activation postimplantation development mouse.Biol. Reprod. 2018; 98: 449-464Google 3.Westerling T. al.Cdk8 essential preimplantation mouse development.Mol. Cell. 2007; 27: 6177-6182Google 4.Rocha P.P. al.Med12 early canonical Wnt Wnt/PCP signaling.Development. 2010; 137: 2723-2731Google Scholar] linked myriad diseases 2).Box 1Vertebrate-specific paralogs subunitsThe conserved among eukaryotes, but CDK8, emerged (Figure I). Each expressed different chromosomes appears be mutually exclusive within [52.Galbraith M.D. al.HIF1A employs CDK8-Mediator stimulate RNAPII elongation response hypoxia.Cell. 2013; 153: 1327-13239Google Scholar]. Comparatively little known about these connections disease have been discovered (Table S1 supplemental information online).CDK8 CDK19 highest sequence identity inhibitors invariably block both proteins. show evidence redundant [109.Sooraj D. al.MED12 BRD4 cooperate sustain cancer growth loss mediator kinase.Mol. 2022; 82: 123-139Google nonredundant functions each has shown kinase-dependent -independent [25.Steinparzer I. al.Transcriptional IFN-gamma require pause release mechanistically distinct functions.Mol. 2019; 76: 485-499Google Scholar,87.Audetat K.A. al.A kinase-independent role cyclin-dependent 19 p53 response.Mol. 2017; 37e00626-16Google Scholar,109.Sooraj Scholar,117.Menzl BCR-ABL1(+) leukemia.Nat. Commun. 10: 4741Google Scholar].The MED12 protein implicated numerous X-linked online) X chromosome, whereas MED12L gene resides chromosome 3. Interestingly, Xist repression (CDK19 no effect) mice [118.Postlmayr A. establishment H3K27me3 development.Development. 2020; 147dev175141Google shows more restricted expression across tissues compared MED12. Whereas necessary [8.Park M.J. al.Oncogenic exon 2 mutations disrupt allosteric cyclin C-CDK8/19.J. Chem. 293: 4870-4882Google Scholar,81.Knuesel M.T. al.The subcomplex histone requires Med12 can independently Mediator.Mol. 2009; 29: 650-661Google Scholar], it unknown whether activates CDK8/19 similarity N-terminal helix I) suggests similar activation.One basic link [10.Knuesel molecular switch co-activator function.Genes Dev. 23: 439-451Google Scholar,11.Tsai K.L. Mediator-CDK8 association Mediator-RNA interaction.Nat. Struct. Mol. 20: 611-619Google Notably, proteomics data suggest modules containing (instead MED13) maintain [39.Ebmeier C.C. Taatjes D.J. Activator-Mediator Mediator-cofactor interactions.Proc. Natl. Acad. Sci. U. S. 107: 11283-11288Google Scholar,119.Sato set consensus identified multidimensional identification technology.Mol. 2004; 14: 685-691Google Moreover, ubiquitylated FBW7, initiates dissociation degradation [110.Davis M.A. SCF-Fbw7 ubiquitin ligase degrades Mediator.Genes 151-156Google Clinical similar, not identical, biological roles online).Box 2Mediator diseaseMutations cause disability online), broadly grouped into two categories: neurological/developmental disorders (reviewed [7.Srivastava Kulshreshtha R. Insights clinical relevance subunit, diseases.J. Physiol. 2021; 236: 3163-3177Google Scholar]). In addition, wide range cancers subunits, summarized recent reviews [121.Dannappel M.V. al.Molecular vivo modules.Front. 6: 171Google Scholar,122.Roninson I.B. al.Identifying impacted CDK8/19.Cells. 8: 821Google Scholar].Three medically related intellectual/developmental syndromes MED12: Opitz-Kaveggia, Lujan, Ohdo syndrome. Furthermore, domains associated intellectual exhibit comparable phenotypes individuals online). introduction could compensate deletion Drosophila, mutant neurological not, resulting seizures reduced fitness surviving flies [123.Chung H.L. al.De novo variants syndrome involving epileptic encephalopathy.Am. J. Hum. Genet. 106: 717-725Google Likewise, induced pathogenic mutants resulted developmental defects [124.Tian al.Somatic de germline MEDs neural tube defects.Front. 9641831Google These results disease-associated CDK19.Mutations nonmalignant uterine leiomyoma most well-studied changes enhancer-promoter looping architecture [79.Moyo M.B. al.Altered landscape engagement underlie dysregulation leiomyomas.Nat. 11: 1019Google negatively Scholar,9.Turunen M. al.Uterine leiomyoma-linked mediator-associated CDK activity.Cell Rep. 7: 654-660Google Such consistent regulation super-enhancer [67.Kuuluvainen E. al.Depletion represses superenhancer-associated genes colon cells.Mol. 38e00573-17Google Scholar,74.Pelish H.E. inhibition further super-enhancer-associated AML.Nature. 2015; 526: 273-276Google Scholar,75.Lynch C.J. al.Global hyperactivation stabilizes naive pluripotency kinases.Nat. 22: 1223-1238Google Scholar].Targeting therapeutic benefit remains work progress, novel strategies continue emerge. Firestein lab showed bromodomain extraterminal domain (BET) (e.g., JQ1) may complement + certain compensatory increases occupancy BET were observed double knockout cells (HCT116 DLD1), suggesting cooperativity agreement other studies [51.Donner A.J. al.CDK8 positive serum network.Nat. 17: 194-201Google Scholar,125.Bhagwat A.S. al.BET releases select cis-regulatory elements.Cell 2016; 15: 519-530Google activation. One Mutations Three Targeting Although current structural only CDK8-CCNC dimer [5.Schneider E.V. CDK8/CycC implicates specificity CDK/cyclin family reveals deep pocket binder.J. 2011; 412: 251-266Google cryogenic electron microscopy (cryoEM) (Saccharomyces cerevisiae) was recently determined Tsai [6.Li Y.C. al.Structure noncanonical Cdk8 mechanism Argonaute-containing module.Sci. Adv. 7eabd4484Google This provided first high-resolution large Med13 subunits. key module. N terminus interacts Cdk8–Ccnc 1). mutated variety clustering around residues 36–44 Structural coworkers occupy complex. otherwise disordered loop, allows substrate access active site Additionally, prior Boyer oncogenic model Med12-dependent likely humans. While details available, Cramer completed crosslinking-mass spectrometry analysis (S. CDK-Mediator [12.Osman II.J. 296100734Google extensive Mediator, including and/or Med19 Med10, Med10 reside hook [13.Zhao H. Tail core.Nat. 12: 1355Google represents interface TFIIH-associated later). this review, some considering past context results. enables cell cascades help 'reprogram' patterns changing conditions. then discuss module-dependent stages (initiation, pausing, elongation) new clarified expanded biochemical cell-based experiments. Finally, represent powerful elements coordinate type- programs outline contribute looping. Throughout, areas understanding limited conclude open questions future research. genome-wide, remodelers, way, serve 'master regulators' pre-initiation (PIC) Activation causes phosphorylation nuclear localization 2). As examples: (i) interferon-induced STAT triggers their allow target activation, (ii) ELK1 phosphorylated during MAPK pathway enhances ELK1-dependent [14.Balamotis al.Complexity domain-Mediator interface.Sci. Signal. 2: ra20Google representative examples, endpoints cascades. Importantly, common targets kinases later), yielding direct signaling. Coordination evident ancient metabolism. Signaling metabolic integrated interdependent, such will trigger adaptation, vice versa 2) [15.Zhu Thompson C.B. Metabolic proliferation.Nat. Rev. 436-450Google flux directly enzymes phosphorylation), they modulate well. organisms cerevisiae, coordinates nutrients [16.Khakhina al.Med13p prevents mitochondrial fission programmed death retention C.Mol. 25: 2807-2816Google 17.Lindsay A.K. al.Analysis Candida albicans defective reveal metabolism biofilm formation.PLoS 10e1004567Google 18.Mousley sterol-binding endosomal lipid TOR nitrogen sensing.Cell. 2012; 148: 702-715Google via [19.Hirst al.GAL4 regulated holoenzyme-associated SRB10/CDK8.Mol. 1999; 3: 673-678Google Scholar,20.Nelson C. al.Srb10/Cdk8 filamentous phosphorylating Ste12.Nature. 2003; 421: 187-190Google Similarly, indirectly metazoans modification TFs. cells, phosphorylates major regulators metabolism, SREBP [21.Zhao X. al.Regulation lipogenesis 8-mediated SREBP-1.J. Clin. Invest. 122: 2417-2427Google Notch ICD Scholar,22.Fryer al.Mastermind recruits CycC:Cdk8 phosphorylate notch turnover.Mol. 509-520Google SMAD1/3 [23.Alarcon al.Nuclear CDKs drive Smad turnover BMP TGF-b pathways.Cell. 139: 757-769Google STAT1/3/5a [24.Bancerek STAT1 selectively interferon response.Immunity. 38: 250-262Google insulin, WNT/β-catenin, TGFβ, cascades, respectively. CDK8-dependent stability co

Language: Английский

Citations

79
Spatial mapping of cellular senescence: emerging challenges and opportunities DOI
Aditi U. Gurkar, Akos A. Gerencser, Ana L. Mora

et al.

Nature Aging, Journal Year: 2023, Volume and Issue: 3(7), P. 776 - 790

Published: July 3, 2023

Language: Английский

Citations

76
Hybrid Small-Molecule/Protein Fluorescent Probes DOI
Masafumi Minoshima, Shahi Imam Reja,

Ryu Hashimoto

et al.

Chemical Reviews, Journal Year: 2024, Volume and Issue: 124(10), P. 6198 - 6270

Published: May 8, 2024

Hybrid small-molecule/protein fluorescent probes are powerful tools for visualizing protein localization and function in living cells. These hybrid constructed by diverse site-specific chemical labeling approaches through reactions to exogenous peptide/small tags, enzymatic post-translational modifications, bioorthogonal genetically incorporated unnatural amino acids, ligand-directed reactions. The employed imaging trafficking, conformational changes, bioanalytes surrounding proteins. In addition, facilitate visualization of dynamics at the single-molecule level defined structure with super-resolution imaging. this review, we discuss development bioimaging applications based on hybrids.

Language: Английский

Citations

26
Lamins: The backbone of the nucleocytoskeleton interface DOI Creative Commons

Joan M. Sobo,

Nicholas S. Alagna,

Sean X. Sun

et al.

Current Opinion in Cell Biology, Journal Year: 2024, Volume and Issue: 86, P. 102313 - 102313

Published: Jan. 22, 2024

Language: Английский

Citations

22
Photochemical Mechanisms of Fluorophores Employed in Single‐Molecule Localization Microscopy DOI Creative Commons
Kai Kikuchi, Liam D. Adair, Jiarun Lin

et al.

Angewandte Chemie International Edition, Journal Year: 2022, Volume and Issue: 62(1)

Published: Sept. 30, 2022

Decoding cellular processes requires visualization of the spatial distribution and dynamic interactions biomolecules. It is therefore not surprising that innovations in imaging technologies have facilitated advances biomedical research. The advent super-resolution has empowered researchers with ability to answer long-standing questions about at an entirely new level. Fluorescent probes greatly enhance specificity resolution experiments. Here, we introduce key technologies, a brief discussion on single-molecule localization microscopy (SMLM). We evaluate chemistry photochemical mechanisms fluorescent employed SMLM. This Review provides guidance identification adoption single molecule inspire design next-generation amenable imaging.

Language: Английский

Citations

41
Super-resolution dynamic tracking of cellular lipid droplets employing with a photostable deep red fluorogenic probe DOI
Jianan Dai, Zihan Wu, Di Li

et al.

Biosensors and Bioelectronics, Journal Year: 2023, Volume and Issue: 229, P. 115243 - 115243

Published: March 21, 2023

Language: Английский

Citations

28
Quantitative Single-Molecule Localization Microscopy DOI Creative Commons

Siewert Hugelier,

Patricia Colosi, Melike Lakadamyali

et al.

Annual Review of Biophysics, Journal Year: 2023, Volume and Issue: 52(1), P. 139 - 160

Published: May 9, 2023

Super-resolution fluorescence microscopy allows the investigation of cellular structures at nanoscale resolution using light. Current developments in super-resolution have focused on reliable quantification underlying biological data. In this review, we first describe basic principles techniques such as stimulated emission depletion (STED) and single-molecule localization (SMLM), then give a broad overview methodological to quantify data, particularly those geared toward SMLM We cover commonly used spatial point pattern analysis, colocalization, protein copy number but also more advanced structural modeling, single-particle tracking, biosensing. Finally, provide an outlook exciting new research directions which quantitative might be applied.

Language: Английский

Citations

25
DBlink: dynamic localization microscopy in super spatiotemporal resolution via deep learning DOI
Alon Saguy, Onit Alalouf, Nadav Opatovski

et al.

Nature Methods, Journal Year: 2023, Volume and Issue: 20(12), P. 1939 - 1948

Published: July 27, 2023

Language: Английский

Citations

25