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Cold Spring Harbor Perspectives in... Apr 2010Like their eukaryotic counterparts, bacterial cells have a highly organized internal architecture. Here, we address the question of how proteins localize to particular... (Review)
Review
Like their eukaryotic counterparts, bacterial cells have a highly organized internal architecture. Here, we address the question of how proteins localize to particular sites in the cell and how they do so in a dynamic manner. We consider the underlying mechanisms that govern the positioning of proteins and protein complexes in the examples of the divisome, polar assemblies, cytoplasmic clusters, cytoskeletal elements, and organelles. We argue that geometric cues, self-assembly, and restricted sites of assembly are all exploited by the cell to specifically localize particular proteins that we refer to as anchor proteins. These anchor proteins in turn govern the localization of a whole host of additional proteins. Looking ahead, we speculate on the existence of additional mechanisms that contribute to the organization of bacterial cells, such as the nucleoid, membrane microdomains enriched in specific lipids, and RNAs with positional information.
Topics: Bacteria; Bacterial Proteins; Cytoplasm; Cytoskeleton; Microscopy, Phase-Contrast
PubMed: 20452938
DOI: 10.1101/cshperspect.a000307 -
Critical Reviews in Biochemistry and... Oct 2018Tyrosine kinases were first discovered as the protein products of viral oncogenes. We now know that this large family of metazoan enzymes includes nearly one hundred... (Review)
Review
Tyrosine kinases were first discovered as the protein products of viral oncogenes. We now know that this large family of metazoan enzymes includes nearly one hundred structurally diverse members. Tyrosine kinases are broadly classified into two groups: the transmembrane receptor tyrosine kinases, which sense extracellular stimuli, and the cytoplasmic tyrosine kinases, which contain modular ligand-binding domains and propagate intracellular signals. Several families of cytoplasmic tyrosine kinases have in common a core architecture, the "Src module," composed of a Src-homology 3 (SH3) domain, a Src-homology 2 (SH2) domain, and a kinase domain. Each of these families is defined by additional elaborations on this core architecture. Structural, functional, and evolutionary studies have revealed a unifying set of principles underlying the activity and regulation of tyrosine kinases built on the Src module. The discovery of these conserved properties has shaped our knowledge of the workings of protein kinases in general, and it has had important implications for our understanding of kinase dysregulation in disease and the development of effective kinase-targeted therapies.
Topics: Allosteric Regulation; Animals; Cytoplasm; Evolution, Molecular; Humans; Models, Molecular; Mutation; Protein Conformation; Substrate Specificity; src Homology Domains; src-Family Kinases
PubMed: 30183386
DOI: 10.1080/10409238.2018.1495173 -
Biophysical Journal May 2021
Topics: Cell Nucleus; Cytoplasm; Cytoskeleton; Rheology
PubMed: 33740439
DOI: 10.1016/j.bpj.2021.02.030 -
Cellular Microbiology Nov 2006Mammalian innate immunity stimulates antigen-specific immune responses and acts to control infection prior to the onset of adaptive immunity. Some bacterial pathogens... (Review)
Review
Mammalian innate immunity stimulates antigen-specific immune responses and acts to control infection prior to the onset of adaptive immunity. Some bacterial pathogens replicate within the host cell and are therefore sheltered from some protective aspects of innate immunity such as complement. Here we focus on mechanisms of innate intracellular resistance encountered by bacterial pathogens and how some bacteria can evade destruction by the innate immune system. Major strategies of intracellular antibacterial defence include pathogen compartmentalization and iron limitation. Compartmentalization of pathogens within the host endocytic pathway is critical for generating high local concentrations of antimicrobial molecules, such as reactive oxygen species, and regulating concentrations of divalent cations that are essential for microbial growth. Cytosolic sensing, autophagy, sequestration of essential nutrients and membrane attack by antimicrobial peptides are also discussed.
Topics: Animals; Bacteria; Cytoplasm; Humans; Immunity, Innate; Models, Biological
PubMed: 16939532
DOI: 10.1111/j.1462-5822.2006.00795.x -
Molecular Cell Mar 2019The localization of long noncoding RNAs (lncRNAs) within the cell is the primary determinant of their molecular functions. LncRNAs are often thought of as... (Review)
Review
The localization of long noncoding RNAs (lncRNAs) within the cell is the primary determinant of their molecular functions. LncRNAs are often thought of as chromatin-restricted regulators of gene transcription and chromatin structure. However, a rich population of cytoplasmic lncRNAs has come to light, with diverse roles including translational regulation, signaling, and respiration. RNA maps of increasing resolution and scope are revealing a subcellular world of highly specific localization patterns and hint at sequence-based address codes specifying lncRNA fates. We propose a new framework for analyzing sequencing-based data, which suggests that numbers of cytoplasmic lncRNA molecules rival those in the nucleus. New techniques promise to create high-resolution, transcriptome-wide maps associated with all organelles of the mammalian cell. Given its intimate link to molecular roles, subcellular localization provides a means of unlocking the mystery of lncRNA functions.
Topics: Active Transport, Cell Nucleus; Animals; Cell Nucleus; Chromatin Assembly and Disassembly; Cytoplasm; Gene Expression Regulation; Genetic Techniques; Humans; RNA, Long Noncoding; Signal Transduction
PubMed: 30849394
DOI: 10.1016/j.molcel.2019.02.008 -
Biochimica Et Biophysica Acta.... Aug 2022The presence of DNA in the cytoplasm of tumor cells induces the dendritic cell to produce type-I IFNs. Classically, the presence of foreign DNA in host cells' cytoplasm... (Review)
Review
The presence of DNA in the cytoplasm of tumor cells induces the dendritic cell to produce type-I IFNs. Classically, the presence of foreign DNA in host cells' cytoplasm during viral infection elicits cGAS-STING mediated type-I IFN signaling and cytokine production. It is likely that cytosolic DNA leads to senescence and immune surveillance in transformed cells during the early stages of carcinogenesis. However, multiple factors, such as loss of cell-cycle checkpoint, mitochondrial damage and chromosomal instability, can lead to persistent accumulation of DNA in the cytoplasm of metastatic tumor cells. That is why aberrant activation of the type I IFN pathway is frequently associated with highly aggressive tumors. Intriguingly, two powerful intracellular deoxyribonucleases, DNase2 and TREX1, can target the cytoplasmic DNA for degradation. Yet the tumor cells consistently accumulate cytoplasmic DNA. This review highlights recent work connecting the lack of DNase2 and TREX1 function to innate immune signaling. It also summarizes the possible mechanisms that limit the activity of DNase2 and TREX1 in tumor cells and contributes to chronic inflammation.
Topics: Cytoplasm; Cytosol; DNA; Neoplasms; Signal Transduction
PubMed: 35489653
DOI: 10.1016/j.bbamcr.2022.119278 -
Viruses Aug 2013Nuclear import and export of viral RNA and proteins are critical to the replication cycle of viruses that replicate in the nucleus. Borna disease virus (BDV) is a... (Review)
Review
Nuclear import and export of viral RNA and proteins are critical to the replication cycle of viruses that replicate in the nucleus. Borna disease virus (BDV) is a nonsegmented, negative-strand RNA virus that belongs to the order Mononegavirales. BDV has several distinguishing features, one of the most striking being the site of its replication. BDV RNA is transcribed and replicated in the nucleus, while most other negative-strand RNA viruses replicate in the cytoplasm. Therefore, the nucleocytoplasmic trafficking of BDV macromolecules plays a key role in virus replication. Growing evidence indicates that several BDV proteins, including the nucleoprotein, phosphoprotein, protein X and large protein, contribute to the nucleocytoplasmic trafficking of BDV ribonucleoprotein (RNP). The directional control of BDV RNP trafficking is likely determined by the ratios of and interactions between the nuclear localization signals and nuclear export signals in the RNP. In this review, we present a comprehensive view of several unique mechanisms that BDV has developed to control its RNP trafficking and discuss the significance of BDV RNP trafficking in the replication cycle of BDV.
Topics: Borna disease virus; Cell Nucleus; Cytoplasm; Gene Expression Regulation, Viral; Protein Transport; Viral Proteins; Virus Replication
PubMed: 23965528
DOI: 10.3390/v5081978 -
International Journal of Molecular... Mar 2020Autophagy is an evolutionarily conserved process that occurs in yeast, plants, and animals. Despite many years of research, some aspects of autophagy are still not fully... (Review)
Review
Autophagy is an evolutionarily conserved process that occurs in yeast, plants, and animals. Despite many years of research, some aspects of autophagy are still not fully explained. This mostly concerns the final stages of autophagy, which have not received as much interest from the scientific community as the initial stages of this process. The final stages of autophagy that we take into consideration in this review include the formation and degradation of the autophagic bodies as well as the efflux of metabolites from the vacuole to the cytoplasm. The autophagic bodies are formed through the fusion of an autophagosome and vacuole during macroautophagy and by vacuolar membrane invagination or protrusion during microautophagy. Then they are rapidly degraded by vacuolar lytic enzymes, and products of the degradation are reused. In this paper, we summarize the available information on the trafficking of the autophagosome towards the vacuole, the fusion of the autophagosome with the vacuole, the formation and decomposition of autophagic bodies inside the vacuole, and the efflux of metabolites to the cytoplasm. Special attention is given to the formation and degradation of autophagic bodies and metabolite salvage in plant cells.
Topics: Autophagosomes; Autophagy; Biological Transport; Cytoplasm; Phagosomes; Plant Physiological Phenomena; Proteolysis; Vacuoles
PubMed: 32210003
DOI: 10.3390/ijms21062205 -
Proceedings of the National Academy of... Feb 2022Cells are filled with macromolecules and polymer networks that set scale-dependent viscous and elastic properties to the cytoplasm. Although the role of these parameters...
Cells are filled with macromolecules and polymer networks that set scale-dependent viscous and elastic properties to the cytoplasm. Although the role of these parameters in molecular diffusion, reaction kinetics, and cellular biochemistry is being increasingly recognized, their contributions to the motion and positioning of larger organelles, such as mitotic spindles for cell division, remain unknown. Here, using magnetic tweezers to displace and rotate mitotic spindles in living embryos, we uncovered that the cytoplasm can impart viscoelastic reactive forces that move spindles, or passive objects with similar size, back to their original positions. These forces are independent of cytoskeletal force generators yet reach hundreds of piconewtons and scale with cytoplasm crowding. Spindle motion shears and fluidizes the cytoplasm, dissipating elastic energy and limiting spindle recoils with functional implications for asymmetric and oriented divisions. These findings suggest that bulk cytoplasm material properties may constitute important control elements for the regulation of division positioning and cellular organization.
Topics: Animals; Biomechanical Phenomena; Cell Division; Cytoplasm; Diffusion; Elasticity; Kinetics; Magnetic Phenomena; Microtubules; Mitosis; Organelles; Sea Urchins; Spindle Apparatus; Viscosity
PubMed: 35169074
DOI: 10.1073/pnas.2115593119 -
Biochemistry May 2018Intracellular environments are heterogeneous milieus comprised of macromolecules, osmolytes, and a range of assemblies that include membrane-bound organelles and...
Intracellular environments are heterogeneous milieus comprised of macromolecules, osmolytes, and a range of assemblies that include membrane-bound organelles and membraneless biomolecular condensates. The latter are nonstoichiometric assemblies of protein and RNA molecules. They represent distinct phases and form via intracellular phase transitions. Here, we present insights from recent studies and provide a perspective on how phase transitions that lead to biomolecular condensates might contribute to cellular functions.
Topics: Biophysical Phenomena; Cell Membrane; Cytoplasm; Organelles; Phase Transition; Proteins; RNA
PubMed: 29323488
DOI: 10.1021/acs.biochem.7b01136