Dynamic and cell-specific transport networks for intracellular copper ions

2021 ◽  
Vol 134 (21) ◽  
Author(s):  
Svetlana Lutsenko
Keyword(s):  
Copper Ions ◽  
Regulatory Proteins ◽  
Transport Networks ◽  
Cu Content ◽  
Cell Compartments ◽  
Intracellular Compartments ◽  
Cu Homeostasis ◽  
And Function ◽  
Cellular Compartments ◽  
Intracellular Copper

ABSTRACT Copper (Cu) homeostasis is essential for the development and function of many organisms. In humans, Cu misbalance causes serious pathologies and has been observed in a growing number of diseases. This Review focuses on mammalian Cu(I) transporters and highlights recent studies on regulation of intracellular Cu fluxes. Cu is used by essential metabolic enzymes for their activity. These enzymes are located in various intracellular compartments and outside cells. When cells differentiate, or their metabolic state is otherwise altered, the need for Cu in different cell compartments change, and Cu has to be redistributed to accommodate these changes. The Cu transporters SLC31A1 (CTR1), SLC31A2 (CTR2), ATP7A and ATP7B regulate Cu content in cellular compartments and maintain Cu homeostasis. Increasing numbers of regulatory proteins have been shown to contribute to multifaceted regulation of these Cu transporters. It is becoming abundantly clear that the Cu transport networks are dynamic and cell specific. The comparison of the Cu transport machinery in the liver and intestine illustrates the distinct composition and dissimilar regulatory response of their Cu transporters to changing Cu levels.

scholarly journals A subcellular atlas of Toxoplasma reveals the functional context of the proteome

2020 ◽  
Author(s):  
Konstantin Barylyuk ◽  
Ludek Koreny ◽  
Huiling Ke ◽  
Simon Butterworth ◽  
Oliver M. Crook ◽  
...  
Keyword(s):  
Subcellular Location ◽  
Host Defenses ◽  
Apicomplexan Parasites ◽  
Cell Compartments ◽  
Considerable Success ◽  
Evolutionary Trajectories ◽  
Functional Context ◽  
And Function ◽  
Cellular Compartments ◽  
Non Destructive

ABSTRACTApicomplexan parasites cause major human disease and food insecurity. They owe their considerable success to novel, highly specialized cell compartments and structures. These adaptations drive their recognition and non-destructive penetration of host’s cells and the elaborate reengineering of these cells to promote growth, dissemination, and the countering of host defenses. The evolution of unique apicomplexan cellular compartments is concomitant with vast proteomic novelty that defines these new cell organizations and their functions. Consequently, half of apicomplexan proteins are unique and uncharacterized, and these cells are, therefore, very poorly understood. Here, we determine the steady-state subcellular location of thousands of proteins simultaneously within the globally prevalent apicomplexan parasite Toxoplasma gondii. This provides unprecedented comprehensive molecular definition to these cells and their novel compartments, and these data reveal the spatial organizations of protein expression and function, adaptation to hosts, and the underlying evolutionary trajectories of these pathogens.

scholarly journals Influence of fluorophore and linker length on the localization and trafficking of fluorescent sterol probes

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Jarmila Králová ◽  
Michal Jurášek ◽  
Lucie Mikšátková ◽  
Anna Marešová ◽  
Jan Fähnrich ◽  
...  
Keyword(s):  
Genetic Mutation ◽  
Cell Permeability ◽  
Specific Cell ◽  
Cell Compartments ◽  
Intracellular Compartments ◽  
Resolution Imaging ◽  
Intracellular Labelling ◽  
Kinetics Of Uptake ◽  
Kinetics Of ◽  
Derivatives Of

AbstractFluorescent sterol probes, comprising a fluorophore connected to a sterol backbone by means of a linker, are promising tools for enabling high-resolution imaging of intracellular cholesterol. In this study, we evaluated how the size of the linker, site of its attachment and nature of the fluorophore, affect the localization and trafficking properties of fluorescent sterol probes. Varying lengths of linker using the same fluorophore affected cell penetration and retention in specific cell compartments. A C-4 linker was confirmed as optimal. Derivatives of heterocyclic sterol precursors attached with identical C-4 linker to different fluorophores at diverse positions also showed significant differences in their binding properties to various intracellular compartments and kinetics of trafficking. Two novel red-emitting probes with good cell permeability, fast intracellular labelling and slightly different distribution displayed very promising characteristics for sterol probes. These probes also strongly labelled endo/lysosomal compartment in cells with pharmacologically disrupted cholesterol transport, or with a genetic mutation of cholesterol transporting protein NPC1, that overlapped with filipin staining of cholesterol. Overall, the present study demonstrates that the physicochemical properties of the fluorophore/linker pairing determine the kinetics of uptake and distribution and subsequently influence the applicability of final probes.

scholarly journals Alterations in mRNA levels, expression, and function of GTP-binding regulatory proteins in adipocytes from obese mice (C57BL/6J-ob/ob)

1991 ◽  
Vol 266 (24) ◽  
pp. 15949-15955
Author(s):  
T.W. Gettys ◽  
V. Ramkumar ◽  
R.J. Uhing ◽  
L. Seger ◽  
I.L. Taylor
Keyword(s):  
Regulatory Proteins ◽  
Mrna Levels ◽  
Obese Mice ◽  
Gtp Binding ◽  
And Function

scholarly journals Saccharomyces cerevisiae Expresses Three Functionally Distinct Homologues of the Nramp Family of Metal Transporters

2000 ◽  
Vol 20 (21) ◽  
pp. 7893-7902 ◽  
Author(s):  
Matthew E. Portnoy ◽  
Xiu Fen Liu ◽  
Valeria Cizewski Culotta
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Yeast Cells ◽  
Manganese Ions ◽  
Iron Starvation ◽  
Metal Transporters ◽  
Cellular Accumulation ◽  
Metal Treatment ◽  
Intracellular Vesicles ◽  
And Function ◽  
Cellular Compartments

ABSTRACT The baker's yeast Saccharomyces cerevisiae expresses three homologues of the Nramp family of metal transporters: Smf1p, Smf2p, and Smf3p, encoded by SMF1, SMF2, andSMF3, respectively. Here we report a comparative analysis of the yeast Smf proteins at the levels of localization, regulation, and function of the corresponding metal transporters. Smf1p and Smf2p function in cellular accumulation of manganese, and the two proteins are coregulated by manganese ions and the BSD2 gene product. Under manganese-replete conditions, Bsd2p facilitates trafficking of Smf1p and Smf2p to the vacuole, where these transport proteins are degraded. However, Smf1p and Smf2p localize to distinct cellular compartments under metal starvation: Smf1p accumulates at the cell surface, while Smf2p is restricted to intracellular vesicles. The third Nramp homologue, Smf3p, is quite distinctive. Smf3p is not regulated by Bsd2p or by manganese ions and is not degraded in the vacuole. Instead, Smf3p is down-regulated by iron through a mechanism that does not involve transcription or protein stability. Smf3p localizes to the vacuolar membrane independently of metal treatment, and yeast cells lacking Smf3p show symptoms of iron starvation. We propose that Smf3p helps to mobilize vacuolar stores of iron.

scholarly journals Multiple cellular compartments engagement in Nicotiana benthamiana-peanut stunt virus-satRNA interactions revealed by systems biology approach

2021 ◽  
Author(s):  
Barbara Wrzesińska ◽  
Agnieszka Zmienko ◽  
Lam Dai Vu ◽  
Ive De Smet ◽  
Aleksandra Obrępalska-Stęplowska
Keyword(s):  
Virus Infection ◽  
Nicotiana Benthamiana ◽  
Cellular Localization ◽  
Plant Interactions ◽  
Satellite Rna ◽  
Functional Connections ◽  
Cell Compartments ◽  
Wide Range ◽  
Peanut Stunt Virus ◽  
Cellular Compartments

Abstract Key message PSV infection changed the abundance of host plant’s transcripts and proteins associated with various cellular compartments, including ribosomes, chloroplasts, mitochondria, the nucleus and cytosol, affecting photosynthesis, translation, transcription, and splicing. Abstract Virus infection is a process resulting in numerous molecular, cellular, and physiological changes, a wide range of which can be analyzed due to development of many high-throughput techniques. Plant RNA viruses are known to replicate in the cytoplasm; however, the roles of chloroplasts and other cellular structures in the viral replication cycle and in plant antiviral defense have been recently emphasized. Therefore, the aim of this study was to analyze the small RNAs, transcripts, proteins, and phosphoproteins affected during peanut stunt virus strain P (PSV-P)–Nicotiana benthamiana interactions with or without satellite RNA (satRNA) in the context of their cellular localization or functional connections with particular cellular compartments to elucidate the compartments most affected during pathogenesis at the early stages of infection. Moreover, the processes associated with particular cell compartments were determined. The ‘omic’ results were subjected to comparative data analyses. Transcriptomic and small RNA (sRNA)–seq data were obtained to provide new insights into PSV-P–satRNA–plant interactions, whereas previously obtained proteomic and phosphoproteomic data were used to broaden the analysis to terms associated with cellular compartments affected by virus infection. Based on the collected results, infection with PSV-P contributed to changes in the abundance of transcripts and proteins associated with various cellular compartments, including ribosomes, chloroplasts, mitochondria, the nucleus and the cytosol, and the most affected processes were photosynthesis, translation, transcription, and mRNA splicing. Furthermore, sRNA-seq and phosphoproteomic analyses indicated that kinase regulation resulted in decreases in phosphorylation levels. The kinases were associated with the membrane, cytoplasm, and nucleus components.

The asialoglycoprotein receptor: relationships between structure, function, and expression

1995 ◽  
Vol 75 (3) ◽  
pp. 591-609 ◽  
Author(s):  
R. J. Stockert
Keyword(s):  
Translational Regulation ◽  
Chemotherapeutic Agents ◽  
Asialoglycoprotein Receptor ◽  
Receptor Expression ◽  
Coated Pits ◽  
Receptor Mediated Endocytosis ◽  
Intracellular Compartments ◽  
Foreign Genes ◽  
And Function ◽  
A Site

Transport of macromolecules into the cell by receptor-mediated endocytosis follows a complex series of intracellular transfers, passing through distinct environments. The asialoglycoprotein receptor is a prototype of the class of receptors that constitutively enters cells via coated pits and delivers ligand to these intracellular compartments. In addition to being a model of receptor-mediated endocytosis, the presence of the receptor on hepatocytes provides a membrane-bound active site for cell-to-cell interactions, has made possible the selective targeting of chemotherapeutic agents and foreign genes, and has also been implicated as a site mediating hepatitis B virus uptake. Regulated expression of receptor subunits and their intracellular trafficking during biosynthesis and endocytosis has provided insights into the relationship of receptor structure to its overall function. As a marker of hepatocellular differentiation, its study has uncovered a unique response to intracellular guanosine 3',5'-cyclic monophosphate and translational regulation of the receptor. In this review, an overview of these diverse findings is provided in an attempt to relate the various aspects of structure and function as they impact on receptor expression.

scholarly journals Three C. elegans Rac proteins and several alternative Rac regulators control axon guidance, cell migration and apoptotic cell phagocytosis

Development ◽  
2001 ◽  
Vol 128 (22) ◽  
pp. 4475-4488 ◽  
Author(s):  
Erik A. Lundquist ◽  
Peter W. Reddien ◽  
Erika Hartwieg ◽  
H. Robert Horvitz ◽  
Cornelia I. Bargmann
Keyword(s):  
Cell Migration ◽  
Axon Guidance ◽  
Apoptotic Cell ◽  
Regulatory Proteins ◽  
Axon Pathfinding ◽  
C Elegans ◽  
Cell Corpse ◽  
And Function ◽  
Redundant Functions ◽  
Caenorhabditis Elegans Genome

The Caenorhabditis elegans genome contains three rac-like genes, ced-10, mig-2, and rac-2. We report that ced-10, mig-2 and rac-2 act redundantly in axon pathfinding: inactivating one gene had little effect, but inactivating two or more genes perturbed both axon outgrowth and guidance. mig-2 and ced-10 also have redundant functions in some cell migrations. By contrast, ced-10 is uniquely required for cell-corpse phagocytosis, and mig-2 and rac-2 have only subtle roles in this process. Rac activators are also used differentially. The UNC-73 Trio Rac GTP exchange factor affected all Rac pathways in axon pathfinding and cell migration but did not affect cell-corpse phagocytosis. CED-5 DOCK180, which acts with CED-10 Rac in cell-corpse phagocytosis, acted with MIG-2 but not CED-10 in axon pathfinding. Thus, distinct regulatory proteins modulate Rac activation and function in different developmental processes.

scholarly journals Intergenic RNA mainly derives from nascent transcripts of known genes

2020 ◽  
Author(s):  
Agostini Federico ◽  
Zagalak Julian ◽  
Attig Jan ◽  
Ule Jernej ◽  
Nicholas M. Luscombe
Keyword(s):  
Rna Polymerase Ii ◽  
Human Genome ◽  
Genomic Context ◽  
Alternative Processing ◽  
Intergenic Regions ◽  
Transcriptional Units ◽  
And Function ◽  
Cellular Compartments ◽  
Nascent Transcripts ◽  
Transcriptional Start Sites

AbstractBackgroundEukaryotic genomes undergo pervasive transcription, leading to the production of many types of stable and unstable RNAs. Transcription is not restricted to regions with annotated gene features but includes almost any genomic context. Currently, the source and function of most RNAs originating from intergenic regions in the human genome remains unclear.ResultsWe hypothesised that many intergenic RNA can be ascribed to the presence of as-yet unannotated genes or the ‘fuzzy’ transcription of known genes that extends beyond the annotated boundaries. To elucidate the contributions of these two sources, we assembled a dataset of >2.5 billion publicly available RNA-seq reads across 5 human cell lines and multiple cellular compartments to annotate transcriptional units in the human genome. About 80% of transcripts from unannotated intergenic regions can be attributed to the fuzzy transcription of existing genes; the remaining transcripts originate mainly from putative long non-coding RNA loci that are rarely spliced. We validated the transcriptional activity of these intergenic RNA using independent measurements, including transcriptional start sites, chromatin signatures, and genomic occupancies of RNA polymerase II in various phosphorylation states. We also analysed the nuclear localisation and sensitivities of intergenic transcripts to nucleases to illustrate that they tend to be rapidly degraded either ‘on-chromatin’ by XRN2 or ‘off-chromatin’ by the exosome.ConclusionsWe provide a curated atlas of intergenic RNAs that distinguishes between alternative processing of well annotated genes from independent transcriptional units based on the combined analysis of chromatin signatures, nuclear RNA localisation and degradation pathways.

Analysis of Ca2+ uptake into the smooth endoplasmic reticulum of permeabilised sternal epithelial cells during the moulting cycle of the terrestrial isopodPorcellio scaber

2002 ◽  
Vol 205 (13) ◽  
pp. 1935-1942 ◽  
Author(s):  
Monica Hagedorn ◽  
Andreas Ziegler
Keyword(s):  
Endoplasmic Reticulum ◽  
Epithelial Cells ◽  
Smooth Endoplasmic Reticulum ◽  
Cyclopiazonic Acid ◽  
Crystal Formation ◽  
Porcellio Scaber ◽  
Intracellular Compartments ◽  
Electron Microscopical ◽  
And Function ◽  
Moulting Cycle

SUMMARYIn terrestrial isopods, large amounts of Ca2+ are transported across anterior sternal epithelial cells during moult-related deposition and resorption of CaCO3 deposits. Because of its toxicity and function as a second messenger, resting cytosolic Ca2+ levels must be maintained below critical concentrations during epithelial Ca2+transport, raising the possibility that organelles play a role during Ca2+ transit. We therefore studied the uptake of Ca2+into Ca2+-sequestering organelles by monitoring the formation of birefringent calcium oxalate crystals in permeabilised anterior and posterior sternal epithelium cells of Porcellio scaber during Ca2+-transporting and non-transporting stages of the moulting cycle using polarised-light microscopy. The results indicate ATP-dependent uptake of Ca2+ into organelles. Half-maximal crystal growth at a Ca2+ activity, aCa, of 0.4 μmol l-1 and blockade by cyclopiazonic acid suggest Ca2+uptake into the smooth endoplasmic reticulum by the smooth endoplasmic reticulum Ca2+-ATPase. Analytical electron microscopical techniques support this interpretation by revealing the accumulation of Ca2+-containing crystals in smooth membranous intracellular compartments. A comparison of different moulting stages demonstrated a virtual lack of crystal formation in the early premoult stage and a significant fivefold increase between mid premoult and the Ca2+-transporting stages of late premoult and intramoult. These results suggest a contribution of the smooth endoplasmic reticulum as a transient Ca2+ store during intracellular Ca2+ transit.

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