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Results for “envelope homeostasis”

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At least 19 recordsLinked to original sources
PubMed2006

The orphan response regulator DigR is required for synthesis of extracellular matrix fibrils in Myxococcus xanthus.

In Myxococcus xanthus, two-component systems have crucial roles in regulating motility behavior and development. Here we describe an orphan response regulator, consisting of an N-terminal receiver domain and a C-terminal DNA binding domain, which is required for A and type IV pilus-dependent gliding motility. Genetic evidence suggests that phosphorylation of the conserved, phosphorylatable aspartate residue in the receiver domain is required for DigR activity. Consistent with the defect in type IV pilus-dependent motility, a digR mutant is slightly reduced in type IV pilus biosynthesis, and the composition of the extracellular matrix fibrils is abnormal, with an increased content of polysaccharides and decreased accumulation of the FibA metalloprotease. By using genome-wide transcriptional profiling, 118 genes were identified that are directly or indirectly regulated by DigR. These 118 genes include only 2, agmQ and cheY4, previously implicated in A and type IV pilus-dependent motility, respectively. In silico analyses showed that 36% of the differentially expressed genes are likely to encode exported proteins. Moreover, four genes encoding homologs of extracytoplasmic function (ECF) sigma factors, which typically control aspects of cell envelope homeostasis, are differentially expressed in a digR mutant. We suggest that the DigR response regulator has an important function in cell envelope homeostasis and that the motility defects in a digR mutant are instigated by the abnormal cell envelope and abnormal expression of agmQ and cheY4.

Amino Acid Sequence↗
PubMed2004

Control of the alternative sigma factor sigmaE in Escherichia coli.

Signal transduction pathways that communicate information from the cell envelope to the cytoplasm of bacteria are crucial to maintain cell envelope homeostasis. In Escherichia coli, one of the key pathways that ensures the integrity of the cell envelope during stress and normal growth is controlled by the alternative sigma factor sigmaE. Recent studies have elucidated the signal transduction pathway that activates sigmaE in response to misfolded outer membrane porins. Unfolded porins trigger the degradation of the sigmaE-specific antisigma factor RseA by the sequential action of two inner membrane proteases, leading to release of sigmaE from RseA, and induction of the stress response. This mechanism of signal transduction, regulated intramembrane proteolysis, is used in transmembrane signaling pathways from bacteria to humans.

Escherichia coli↗
PubMed2026

The SigD regulon of Mycobacterium abscessus determines cell envelope composition and antibiotic susceptibility.

A major determinant of the exceptional intrinsic resistance of M. abscessus is the lipid-rich cell envelope, yet the regulatory systems that remodel envelope-associated pathways remain poorly defined. Here, we determine the σD regulon in M. abscessus and establish its role in cell envelope homeostasis and intrinsic resistance to hydrophobic antibiotics. RNA-Seq analysis of a MabΔsigD mutant identified 447 differentially expressed genes, while ChIP-Seq mapped 72 σD binding sites and defined a conserved promoter motif (GTAACA/G-N16-CGAT). Using a combination of σD binding, motif orientation and expression data, we identified a core set of directly regulated genes, distinct from what was previously observed in M. tuberculosis, many of which encode proteins involved in envelope-associated functions. These include loci involved in trehalose polyphleate (TPP) biosynthesis, the antigen 85 complex and peptidoglycan remodeling enzymes. Deletion of sigD resulted in a significant reduction in TPPs in the cell envelope and an increase in ethidium bromide accumulation. Consistent with these changes, loss of σD selectively sensitized M. abscessus to hydrophobic antibiotics, including rifampicin and tigecycline. Deletion of mmpL10, which is required for transport of TPP precursors, recapitulated the drug sensitivity of MabΔsigD, implicating envelope composition as a key effector of the phenotype. Expression of the σD regulon further increased during starvation and in response to SDS, isoniazid, and ethambutol, mediated by degradation of RsdA, consistent with a role in stress-responsive envelope adaptation. Together, these findings demonstrate σD is active during logarithmic growth in rich media where it regulates the expression of envelope-associated genes that influence envelope permeability and basal level susceptibility to hydrophobic antibiotics; its activity further increases in response to cell envelope stress, presumably promoting envelope remodeling to counteract damage.

Regulon↗
PubMed2005

Characterization of six lipoproteins in the sigmaE regulon.

In Escherichia coli, sigma(E) regulon functions are required for envelope homeostasis during stress and are essential for viability under all growth conditions. The E. coli genome encodes approximately 100 lipoproteins, and 6 of these are regulated by sigma(E). Phenotypes associated with deletion of each of these lipoproteins are the subject of this report. One lipoprotein, YfiO, is essential for cellular viability. However, overexpression of this protein is not sufficient to alleviate the requirement of sigma(E) for viability, suggesting that the sigma(E) regulon provides more than one essential function. The remaining five lipoproteins in the sigma(E) regulon are nonessential; cells are viable even when all five are removed simultaneously. Deletion of three nonessential lipoprotein genes (nlpB, yraP, ygfL) results in the exhibition of phenotypes that suggest they are important for maintenance of the integrity of the cell envelope. deltanlpB cells are selectively sensitive to rifampin; deltayraP cells are selectively sensitive to sodium dodecyl sulfate. Such selective sensitivity has not been previously reported. Both deltayraP and deltanlpB are synthetically lethal with surA::Cm, which encodes a periplasmic chaperone and PPIase, suggesting that NlpB and YraP play roles in a periplasmic folding pathway that functions in parallel with that of SurA. Finally, the deltayfgL mutant exhibits a broad range of envelope defects, including sensitivity to several membrane-impermeable agents, an altered outer membrane protein profile, synthetic lethality with both surA::Cm and deltafkpA::Cm strains, and sensitivity to a bactericidal permeability-increasing peptide. We suggest that this lipoprotein performs a very important but as-yet-unknown function in maintaining the integrity of the cell envelope.

Amino Acid Sequence↗
PubMed2002

Antibiotics that inhibit cell wall biosynthesis induce expression of the Bacillus subtilis sigma(W) and sigma(M) regulons.

Bacillus subtilis encodes seven extracytoplasmic function (ECF) sigma factors. The sigma(W) regulon includes functions involved in detoxification and protection against antimicrobials, whereas sigma(M) is essential for growth at high salt concentrations. We now report that antibiotics that inhibit cell wall biosynthesis induce both sigma(W) and sigma(M) regulons as monitored using DNA microarrays. Induction of selected sigma(W)-dependent genes was confirmed using lacZ reporter fusions and Northern blot analysis. The ability of vancomycin to induce the sigma(W) regulon is dependent on both sigma(W) and the cognate anti-sigma, RsiW, but is independent of the transition state regulator AbrB. These results suggest that the membrane-localized RsiW anti-sigma(W) factor mediates the transcriptional response to cell wall stress. Our findings are consistent with the idea that one function of ECF sigma factors is to coordinate antibiosis stress responses and cell envelope homeostasis.

Anti-Bacterial Agents↗
PubMed2004

A probable Na+(K+)/H+ exchanger on the chloroplast envelope functions in pH homeostasis and chloroplast development in Arabidopsis thaliana.

Electroneutral monovalent cation/proton antiport across the chloroplast envelope has been shown previously to have an important regulatory effect on stromal pH and thereby on photosynthetic carbon reduction. Here we report that an Arabidopsis nuclear gene, AtCHX23, encodes a putative Na(+)(K(+))/H(+) exchanger and functions in the adjustment of pH in the cytosol and possibly in maintaining a high pH level in the chloroplast stroma. The AtCHX23 protein is localized in the chloroplast envelope. Plastids from chx23 mutants had straight thylakoids but lacked grana lamellae. chx23 mutant leaves were pale yellow and had a much reduced chlorophyll content. The chlorophyll content of chx23 was increased by growing in medium at low (4.0) pH and decreased by growing at high (7.0) pH. The cytosolic pH in the leaves of the mutant was significantly higher than that in the wild type. chx23 mutants displayed a high sensitivity to NaCl. Together, these data indicate that CHX23 is a probable chloroplast Na(+)(K(+))/H(+) exchanger important for pH homeostasis and chloroplast development and function.

Antiporters↗
PubMed2025

TamL is a Key Player of the Outer Membrane Homeostasis in Bacteroidota.

In Proteobacteria, the outer membrane protein TamA and the inner membrane-anchored protein TamB form the Translocation and Assembly Module (TAM) complex, which facilitates the transport of autotransporters, virulence factors, and likely lipids across the two membranes. In Bacteroidota, TamA is replaced by TamL, a TamA-like lipoprotein with a lipid modification at its N-terminus that likely anchors it to the outer membrane. This structural difference suggests that TamL may have a distinct function compared to TamA. However, the role of TAM in bacterial phyla other than Proteobacteria remains unexplored. Our study aimed to elucidate the function of TamL in Flavobacterium johnsoniae, an environmental Bacteroidota. Unlike its homologs in Proteobacteria, we found that TamL and TamB are essential in F. johnsoniae. Through genetic, phenotypic, proteomic, and lipidomic analyses, we show that TamL depletion severely compromises outer membrane integrity, as evidenced by reduced cell viability, altered cell shape, increased susceptibility to membrane-disrupting agents, and elevated levels of outer membrane lipoproteins. Notably, we did not observe an overall decrease in the levels of β-barrel outer membrane proteins, nor substantial alterations in outer membrane lipid composition. By pull-down assays, we found TamL co-purifying with TamB in F. johnsoniae, suggesting an interaction. Furthermore, we found that while TamL and TamB monocistronic genes are conserved among Bacteroidota, only some species encode multiple TamL, TamB and TamA proteins. To our knowledge, this study is the first to provide functional insights into a TAM subunit beyond Proteobacteria.

Bacterial Outer Membrane Proteins↗
PubMed2005

The expression profile of Escherichia coli K-12 in response to minimal, optimal and excess copper concentrations.

The gene expression profile of Escherichia coli K-12 MG1655 grown in minimal medium supplemented with elevated copper concentrations (as copper-glycine) has been analysed using whole-genome oligonucleotide microarrays. At 750 muM copper-glycine, the expression of both the cue and cus copper-export systems is evident. At near-lethal copper concentrations (2 mM copper-glycine), the expression of these two regulons increases significantly. Other regulons with increased transcription in response to elevated concentrations of copper-glycine include those for the superoxide stress response, iron homeostasis, and envelope stress. Furthermore, a variety of ORFs with decreased expression in response to increased copper-glycine has been identified, including the zinc ABC transporter and genes involved in the chemotactic response.

Bacterial Proteins↗
PubMed1995

HIV-1 envelope proteins gp120 and gp160 potentiate NMDA-induced [Ca2+]i increase, alter [Ca2+]i homeostasis and induce neurotoxicity in human embryonic neurons.

The envelope glycoprotein gp120 of the human immunodeficiency virus HIV-1 has been proposed to cause neuron death in developing murine hippocampal cultures and rat retinal ganglion cells. In the present study, cultured human embryonic cerebral and spinal neurons from 8- to 10-week-old embryos were used to study the neurotoxic effect of gp120 and gp160. Electrophysiological properties as well as N-methyl-D-aspartate (NMDA)-induced current were recorded from neurons maintained in culture for 10-30 days. Neither voltage-activated sodium or calcium currents nor NMDA-induced currents were affected by exposure of neurons to 250 pM gp120 or gp160. In contrast, when neurons were subjected to photometric measurements using the calcium dye indo-1 to monitor the intracellular free Ca2+ concentration ([Ca2+])i, gp120 and gp160 (20-250 pM) potentiated the large rises in [Ca2+]i induced by 50 microM NMDA. The potentiation of NMDA-induced Ca2+ responses required the presence of Ca2+ in the medium, and was abolished by the NMDA antagonist D-2-amino-5-phosphonovalerate (AP5) and the voltage-gated Ca2+ channel inhibitor nifedipine. Moreover, exposure of a subpopulation of spinal neurons (25% of the cells tested) to 20-250 pM gp120 or gp160 resulted in an increase in [Ca2+]i that followed three patterns: fluctuations not affected by AP5, a single peak, and the progressive and irreversible rise of [Ca2+]i. The neurotoxicity of picomolar doses of gp120 and gp160 cultures was estimated by immunofluorescence and colorimetric assay. Treatment of cultures with AP5 or nifedipine reduced gp120-induced toxicity by 70 and

Calcium↗
PubMed2006

Temporal transcriptomic analysis as Desulfovibrio vulgaris Hildenborough transitions into stationary phase during electron donor depletion.

Desulfovibrio vulgaris was cultivated in a defined medium, and biomass was sampled for approximately 70 h to characterize the shifts in gene expression as cells transitioned from the exponential to the stationary phase during electron donor depletion. In addition to temporal transcriptomics, total protein, carbohydrate, lactate, acetate, and sulfate levels were measured. The microarray data were examined for statistically significant expression changes, hierarchical cluster analysis, and promoter element prediction and were validated by quantitative PCR. As the cells transitioned from the exponential phase to the stationary phase, a majority of the down-expressed genes were involved in translation and transcription, and this trend continued at the remaining times. There were general increases in relative expression for intracellular trafficking and secretion, ion transport, and coenzyme metabolism as the cells entered the stationary phase. As expected, the DNA replication machinery was down-expressed, and the expression of genes involved in DNA repair increased during the stationary phase. Genes involved in amino acid acquisition, carbohydrate metabolism, energy production, and cell envelope biogenesis did not exhibit uniform transcriptional responses. Interestingly, most phage-related genes were up-expressed at the onset of the stationary phase. This result suggested that nutrient depletion may affect community dynamics and DNA transfer mechanisms of sulfate-reducing bacteria via the phage cycle. The putative feoAB system (in addition to other presumptive iron metabolism genes) was significantly up-expressed, and this suggested the possible importance of Fe2+ acquisition under metal-reducing conditions. The expression of a large subset of carbohydrate-related genes was altered, and the total cellular carbohydrate levels declined during the growth phase transition. Interestingly, the D. vulgaris genome does not contain a putative rpoS gene, a common attribute of the delta-Proteobacteria genomes sequenced to date, and the transcription profiles of other putative rpo genes were not significantly altered. Our results indicated that in addition to expected changes (e.g., energy conversion, protein turnover, translation, transcription, and DNA replication and repair), genes related to phage, stress response, carbohydrate flux, the outer envelope, and iron homeostasis played important roles as D. vulgaris cells experienced electron donor depletion.

Bacterial Proteins↗
PubMed2004

Characterization of a thymus-tropic HIV-1 isolate from a rapid progressor: role of the envelope.

Loss of T cell homeostasis usually precedes the onset of AIDS. We hypothesized that rapid progressors may be transmitted with HIV-1 that is particularly able to perturb T cell homeostasis. To this end, we have tested two transmitted, syncytium-inducing (SI) viral isolates from a rapid progressor in two thymus models. One of the isolates (R3A) exhibited markedly rapid kinetics of replication and thymocyte depletion. These phenotypes mapped to the envelope, as a recombinant NL4-3 virus encoding the R3A envelope had similar phenotypes, even in the absence of nef. Notably, the viruses with high pathogenic activity in the thymus (R3A and NL4-R3A) did not show enhanced replication or cytopathicity in PHA-stimulated PBMCs. Furthermore, NL4-R3A did not enhance replication of the coinfected NL4-3 virus in the thymus, suggesting an intrinsic advantage of the R3A envelope. The R3A envelope showed higher entry activity in infecting human T cells and in depleting CD4+ thymocytes when expressed in trans. These data suggest that SI viruses with unique envelope functions which can overcome barriers to transmission may hasten disease progression by perturbing T cell homeostasis.

Amino Acid Sequence↗
PubMed1997

FeLV envelope protein (gp70) variable region 5 causes alterations in calcium homeostasis and toxicity of neurons.

In humans and animals, retroviruses have been implicated in nervous system disease. Our objective was to characterize the neurotoxicity of a peptide sequence derived from an animal retrovirus, the feline leukemia virus (FeLV). Using a peptide sequence from the subtype FeLV-C envelope protein variable region 5 (VR5), cytotoxicity was demonstrated in studies that evaluated neuronal survival, neurite outgrowth, and alterations in intracellular calcium ion concentration. The FeLV subtype isolate FeLV-CSarma possesses an envelope protein VR5 amino acid sequence that varies by four amino acids from the VR5 amino acid sequence of subtype FeLV-AGlasgow. The polypeptide representing the VR5 of FeLV-CSarma (FeLV-CVR5) is significantly more neurotoxic than the polypeptide sequence representing the VR5 of FeLV-AGlasgow (FeLV-AVR5). FeLV-CVR5 (> or = 3 microM) exposure resulted in significant dose-dependent neurotoxicity. Antibodies to FeLV-CVR5 blocked this effect. Neurite outgrowth was significantly reduced at all tested concentrations (3-12 microM) of FeLV-CVR5, with a 92% reduction in neurite length at 12 microM. FeLV-AVR5 was significantly less neurotoxic with respect to neurite outgrowth than was FeLV-CVR5. The significant reduction in neurotoxicity for FeLV-AVR5 illustrates the importance of the 4-amino-acid difference between it and FeLV-CVR5. Alterations in intracellular calcium ion concentration were associated with this neurotoxicity.

Animals↗
PubMed2005

Osteoarthritis after sports knee injuries.

Recent advances in the knowledge of tissue homeostasis, including the tissue homeostasis theory and the envelope of function theory as proposed by Dye, have greatly increased our knowledge of the pathophysiology of osteoarthrosis after sports knee injuries. The development of these two theories has not only advanced our understanding of the treatment and prevention of osteoarthrosis after acute injuries to the knee, but has also given us guidance as to directions for future research.

Athletic Injuries↗
PubMedDate not supplied

Calcium regulation of nuclear pore permeability.

The nuclear envelope is an integral part of the structural framework of the nucleus, and is involved in organizing intranuclear events. It serves as a selective barrier, actively transporting proteins required for normal nuclear function and exporting RNA. The movement of molecules across the nuclear envelope is critical for cellular homeostasis, and it allows cells to respond to external events. The only known pathway for direct communication between the cytoplasm and the nucleoplasm of a cell is through the nuclear pore complex. In the past decade, rapid advances have been made in elucidating the structure and function of the nuclear pore complex. Yet, researchers are just beginning to identify some of the regulatory mechanisms controlling transport through the pore complex. The nucleus is surrounded by a Ca2+ storage compartment, which sequesters and releases Ca2+ in response to intracellular second messengers, Recent evidence suggests that the nuclear Ca2+ store may indirectly regulate passive diffusion through the nuclear pore complex. The evidence for Ca2+ regulation of the nuclear pore complex will be discussed, along with the introduction of the simplest, testable model to describe the observations.

Animals↗
PubMed2006

Subpopulations of neurons expressing parvalbumin in the human amygdala.

Amygdalar intrinsic inhibitory networks comprise several subpopulations of gamma-aminobutyric acidergic neurons, each characterized by distinct morphological features and clusters of functionally relevant neurochemical markers. In rodents, the calcium-binding proteins parvalbumin (PVB) and calbindin D28k (CB) are coexpressed in large subpopulations of amygdalar interneurons. PVB-immunoreactive (-IR) neurons have also been shown to be ensheathed by perineuronal nets (PNN), extracellular matrix envelopes believed to affect ionic homeostasis and synaptic plasticity. We tested the hypothesis that differential expression of these three markers may define distinct neuronal subpopulations within the human amygdala. Toward this end, triple-fluorescent labeling using antisera raised against PVB and CB as well as biotinylated Wisteria floribunda lectin for detection of PNN was combined with confocal microscopy. Among the 1,779 PVB-IR neurons counted, 18% also expressed CB, 31% were ensheathed in PNN, and 7% expressed both CB and PNN. Forty-four percent of PVB-IR neurons did not colocalize with either CB or PNN. The distribution of each of these neuronal subgroups showed substantial rostrocaudal gradients. Furthermore, distinct morphological features were found to characterize each neuronal subgroup. In particular, significant differences relative to the distribution and morphology were detected between PVB-IR neurons expressing CB and PVB-IR neurons wrapped in PNNs. These results indicate that amygdalar PVB-IR neurons can be subdivided into at least four different subgroups, each characterized by a specific neurochemical profile, morphological characteristics, and three-dimensional distribution. Such properties suggest that each of these neuronal subpopulations may play a specific role within the intrinsic circuitry of the amygdala.

Adult↗
PubMed2006

Oxidative stress in the pathogenesis of skin disease.

Skin is the largest body organ that serves as an important environmental interface providing a protective envelope that is crucial for homeostasis. On the other hand, the skin is a major target for toxic insult by a broad spectrum of physical (i.e. UV radiation) and chemical (xenobiotic) agents that are capable of altering its structure and function. Many environmental pollutants are either themselves oxidants or catalyze the production of reactive oxygen species (ROS) directly or indirectly. ROS are believed to activate proliferative and cell survival signaling that can alter apoptotic pathways that may be involved in the pathogenesis of a number of skin disorders including photosensitivity diseases and some types of cutaneous malignancy. ROS act largely by driving several important molecular pathways that play important roles in diverse pathologic processes including ischemia-reperfusion injury, atherosclerosis, and inflammatory responses. The skin possesses an array of defense mechanisms that interact with toxicants to obviate their deleterious effect. These include non-enzymatic and enzymatic molecules that function as potent antioxidants or oxidant-degrading systems. Unfortunately, these homeostatic defenses, although highly effective, have limited capacity and can be overwhelmed thereby leading to increased ROS in the skin that can foster the development of dermatological diseases. One approach to preventing or treating these ROS-mediated disorders is based on the administration of various antioxidants in an effort to restore homeostasis. Although many antioxidants have shown substantive efficacy in cell culture systems and in animal models of oxidant injury, unequivocal confirmation of their beneficial effects in human populations has proven elusive.

Antioxidants↗
PubMed2000

Omega-hydroxyceramides are required for corneocyte lipid envelope (CLE) formation and normal epidermal permeability barrier function.

Omega-hydroxyceramides (omega-OHCer) are the predominant lipid species of the corneocyte lipid envelope in the epidermis. Moreover, their omega-esterified-derivatives (acylCer) are major components of the stratum corneum extracellular lamellae, which regulate cutaneous permeability barrier function. Because epidermal omega-OHCer appear to be generated by a cytochrome P450-dependent process, we determined the effects of a mechanism-based inhibitor of omega-hydroxylation, aminobenzotriazole (ABT), on epidermal omega-OH Cer formation and barrier function. We first ascertained that ABT, but not hydroxybenzotriazole (OHBT), a chemical relative with no P450 inhibitory activity, inhibited the incorporation of [14C]-acetate into the omega-OH-containing Cer species in cultured human keratinocytes (68.1% +/- 6.9% inhibition versus vehicle-treated controls; p < 0.001), without altering the synthesis of other Cer and fatty acid species. In addition, ABT significantly inhibited the omega-hydroxylation of very long-chain fatty acids in cultured human keratinocytes. Topical application of ABT, but not OHBT, when applied to the skin of hairless mice following acute barrier disruption by tape-stripping, resulted in a significant delay in barrier recovery (e.g., 38.3% delay at 6 h versus vehicle-treated animals), assessed as increased transepidermal water loss. The ABT-induced barrier abnormality was associated with: (i) a significant decrease in the quantities of omega-OHCer in both the unbound and the covalently bound Cer pools; (ii) marked alterations of lamellar body structure and contents; and (iii) abnormal stratum corneum extracellular lamellar membrane structures, with no signs of cellular toxicity. Furthermore, pyridine-extraction of ABT- versus vehicle-treated skin, which removes all of the extracellular lamellae, leaving the covalently attached lipids, showed numerous foci with absent corneocyte lipid envelope in ABT- versus vehicle-treated stratum corneum. These results provide the first direct evidence for the importance of omega-OHCer for epidermal permeability function, and suggest further that acylCer and/or corneocyte lipid envelope are required elements in permeability barrier homeostasis.

Administration, Topical↗