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At least 775 records · Page 43Linked to original sources
PubMed2006

Pyoverdine siderophores: from biogenesis to biosignificance.

Pyoverdines are a group of structurally related siderophores produced by fluorescent Pseudomonas species. Recent genomic and biochemical data have shed new light on the complex molecular steps of pyoverdine biogenesis and explained the chemical diversity of these compounds. In the opportunistic pathogen Pseudomonas aeruginosa, pyoverdine is necessary for infection in several different disease models. The occurrence of pyoverdine-defective strains in chronic infections of patients with cystic fibrosis and the extremely high sequence diversity of genes involved in pyoverdine synthesis and uptake indicate that pyoverdine production is subject to high evolutionary pressure. Pyoverdine-dependent iron transport is also crucial for biofilm development, further expanding the importance of these siderophores in Pseudomonas biology.

Bacterial Proteins↗
PubMed2005

A mutation in the silver gene leads to defects in melanosome biogenesis and alterations in the visual system in the zebrafish mutant fading vision.

Forward genetic screens have been instrumental in defining molecular components of visual function. The zebrafish mutant fading vision (fdv) has been identified in such a screen due to defects in vision accompanied by hypopigmentation in the retinal pigment epithelium (RPE) and body melanocytes. The RPE forms the outer most layer of the retina, and its function is essential for vision. In fdv mutant larvae, the outer segments of photoreceptors are strongly reduced in length or absent due to defects in RPE cells. Ultrastructural analysis of RPE cells reveals dramatic cellular changes such as an absence of microvilli and vesicular inclusions. The retinoid profile is altered as judged by biochemical analysis, arguing for a partial block in visual pigment regeneration. Surprisingly, homozygous fdv vision mutants survive to adulthood and show, despite a persistence of the hypopigmentation, a partial recovery of retinal morphology. By positional cloning and subsequent morpholino knock-down, we identified a mutation in the silver gene as the molecular defect underlying the fdv phenotype. The Silver protein is required for intralumenal fibril formation in melanosomes by amylogenic cleavage. Our data reveal an unexpected link between melanosome biogenesis and the visual system, undetectable in cell culture.

Amino Acid Sequence↗
PubMed2006

Studies on the role of NonA in mRNA biogenesis.

The NonA protein of Drosophila melanogaster is an abundant nuclear protein that belongs to the DBHS (Drosophila behavior, human splicing) protein family. The DBHS proteins bind both DNA and RNA in vitro and have been involved in different aspects of gene expression, including pre-mRNA splicing, transcription regulation and nuclear retention of mRNA. We have used double-stranded RNA interference in Drosophila S2 cells to silence the expression of NonA and to investigate its role in mRNA biogenesis. We show that knockdown of NonA does not affect transcription nor splicing. We demonstrate that NonA forms a complex with the essential nuclear export factor NXF1 in an RNA-dependent manner. We have constructed stable S2 cell lines that express full-length and truncated NXF1 fused to GFP in order to perform fluorescence recovery after photobleaching experiments. We show that knockdown of NonA reduces the intranuclear mobility of NXF1-GFP associated with poly(A)(+) RNA in vivo, while the mobility of the truncated NXF1-GFP that does not bind RNA is not affected. Our data suggest that NonA facilitates the intranuclear mobility of mRNP particles.

Active Transport, Cell Nucleus↗
PubMed2004

Drug-induced increased mitochondrial biogenesis in a liver biopsy.

Oncocytic changes seen in hepatocytes in patients receiving highly active antiretroviral therapy (HAART) are a result of mitochondrial damage. This is the first report that provides the electron microscopy illustration of mitochondrial proliferation as a result of the HAART drug Stavudine (Zerit) hepatotoxicity. The drug's effect on mitochondrial DNA replication leads to depleted mitochondrial-encoded proteins and configurational defects of the mitochondrial inner membrane leading to reduced and abnormal cristae, which house the electron transport chain and elementary bodies. This results in a decrease in the NAD/NADH ratio and reduces oxidative phosphorylation. The shift in the NAD/NADH ratio decreases the rate of fatty acid beta oxidation and oxidation of pyruvate by the Krebs cycle. Decreased oxidation of pyruvate drives it into an alternative pathway to form lactate leading to lactic acidosis. This mitochondrial dysfunction results in a compensatory increase in mitochondrial biogenesis, which results in oncocytic changes of the hepatocytes.

Adult↗
PubMed2004

The PEX Gene Screen: molecular diagnosis of peroxisome biogenesis disorders in the Zellweger syndrome spectrum.

Peroxisome biogenesis disorders in the Zellweger syndrome spectrum (PBD-ZSS) are caused by defects in at least 12 PEX genes required for normal organelle assembly. Clinical and biochemical features continue to be used reliably to assign patients to this general disease category. Identification of the precise genetic defect is important, however, to permit carrier testing and early prenatal diagnosis. Molecular analysis is likely to expand the clinical spectrum of PBD and may also provide data relevant to prognosis and future therapeutic intervention. However, the large number of genes involved has thus far impeded rapid mutation identification. In response, we developed the PEX Gene Screen, an algorithm for the systematic screening of exons in the six PEX genes most commonly defective in PBD-ZSS. We used PCR amplification of genomic DNA and sequencing to screen 91 unclassified PBD-ZSS patients for mutations in PEX1, PEX26, PEX6, PEX12, PEX10, and PEX2. A maximum of 14 reactions per patient identified pathological mutations in 79% and both mutant alleles in 54%. Twenty-five novel mutations were identified overall. The proportion of patients with different PEX gene defects correlated with frequencies previously identified by complementation analysis. This systematic, hierarchical approach to mutation identification is therefore a valuable tool to identify rapidly the molecular etiology of suspected PBD-ZSS disorders.

Algorithms↗
PubMed2001

Mitochondrial alterations caused by defective peroxisomal biogenesis in a mouse model for Zellweger syndrome (PEX5 knockout mouse).

Zellweger syndrome (cerebro-hepato-renal syndrome) is the most severe form of the peroxisomal biogenesis disorders leading to early death of the affected children. To study the pathogenetic mechanisms causing organ dysfunctions in Zellweger syndrome, we have recently developed a knockout-mouse model by disrupting the PEX5 gene, encoding the targeting receptor for most peroxisomal matrix proteins (M Baes, P Gressens, E Baumgart, P Carmeliet, M Casteels, M Fransen, P Evrard, D Fahimi, PE Declercq, D Collen, PP van Veldhoven, GP Mannaerts: A mouse model for Zellweger syndrome. Nat Genet 1997, 17:49-57). In this study, we present evidence that the absence of functional peroxisomes, causing a general defect in peroxisomal metabolism, leads to proliferation of pleomorphic mitochondria with severe alterations of the mitochondrial ultrastructure, changes in the expression and activities of mitochondrial respiratory chain complexes, and an increase in the heterogeneity of the mitochondrial compartment in various organs and specific cell types (eg, liver, proximal tubules of the kidney, adrenal cortex, heart, skeletal and smooth muscle cells, neutrophils). The changes of mitochondrial respiratory chain enzymes are accompanied by a marked increase of mitochondrial manganese-superoxide dismutase, as revealed by in situ hybridization and immunocytochemistry, suggesting increased production of reactive oxygen species in altered mitochondria. This increased oxidative stress induced probably by defective peroxisomal antioxidant mechanisms combined with accumulation of lipid intermediates of peroxisomal beta-oxidation system could contribute significantly to the pathogenesis of multiple organ dysfunctions in Zellweger syndrome.

Adenosine Triphosphate↗
PubMed1998

A novel pathway for cytochromes c biogenesis in chloroplasts.

The cytochromes c are a useful model for the study of the pathways and mechanisms of assembly of the cofactor-containing components of energy transducing membranes. Genetic analyses have identified proteins that are required for the assembly of c-type cytochromes in mitochondria, bacteria and chloroplasts. The components of the pathway operating in fungal and animal mitochondria, i.e. the cytochrome (cyt) c and c1 heme lyases in the intermembrane space, were identified over a decade ago through the study of cytochrome deficiencies in Neurospora crassa and Saccharomyces cerevisiae. More recently, a large number of membrane or membrane-associated components were identified in various alpha- and gamma-proteobacteria as c-type cytochrome assembly factors; they comprise an assembly pathway that is evolutionarily and mechanistically distinct from that in fungal and animal mitochondria. The components function not only in the lyase reaction but also in the delivery and maintenance of the substrates in a state that is suitable for reaction in the bacterial periplasm. Yet a third pathway is required for cytochrome maturation in chloroplasts. Genetic analyses of Chlamydomonas reinhardtii ccs mutants, which are pleiotropically deficient in both the membrane-anchored cytochrome f and the soluble cytochrome c6, revealed a minimum of six loci, plastid ccsA and nuclear CCS1 through CCS5, that are required for the conversion of the chloroplast apocytochromes to their respective holo forms. Sequence analysis of the cloned ccsA and Ccs1 genes indicates that the predicted protein products are integral membrane proteins with homologues in cyanobacteria, some gram-positive bacteria (Bacillus subtilis, Mycobacterium spp.), beta-proteobacteria (Neisseria spp.) and an epsilon-proteobacterium (Helicobacter pylori). CcsA and Ccs1 require each other for accumulation in vivo and are therefore proposed to function in a complex, possibly with the products of some of the other CCS loci. A tryptophan-rich motif, which has been proposed to represent a heme binding site in bacterial cytochrome biogenesis proteins (CcmC and CcmF), is functionally important in plastid CcsA. As is the case for CcmC and CcmF, the tryptophan-rich sequence is predicted to occur in a loop on the p-side of the membrane, where the heme attachment reaction occurs. Conserved histidine residues in the CcsA and Ccs1 may serve as ligands to the heme iron. A multiple alignment of the tryptophan-rich regions of the CcsA-, CcmC- and CcmF-like sequences in the genome databases indicates that they represent three different families.

Amino Acid Sequence↗
PubMed2002

Tep22, a novel testicular expressed gene, is involved in the biogenesis of the acrosome and the midpiece of the sperm tail.

To identify new genes that could be involved in the differentiation and function of male germ cells, we have screened a murine testis cDNA library and isolated a clone that was named Tep22. The gene encoding Tep22 consists of three exons and is localized in the telomeric region of mouse chromosome 12. Expression analyses with RNA from different adult tissues revealed that Tep22 is predominantly expressed in spermatocytes and spermatids of the murine testis. Four Tep22 transcript sizes ranging from 647 to 1122 nucleotides were detected in testes of 15-day-old mice due to variable 5' UTRs, while the open reading frame of Tep22 has a length of 567bp in all transcript forms. Specific antibodies against Tep22 detected an approximately 22kDa band in testicular protein extracts, which was first observed in 18-day-old mice, indicating that Tep22 is translationally repressed for several days. Indirect immunofluorescence and immunoelectron microscopy experiments demonstrate that Tep22 is localized in the acrosomal region of early elongating spermatids, while the surrounding cytoplasm is barely labeled. During further germ cell development, the intensity of the staining in the acrosomal region decreases and is no longer detectable in late stages of elongating spermatids, whereas the amount of the Tep22 protein increases in the cytoplasm. Finally, Tep22 is incorporated into the midpiece of spermatids and is also present in the mitochondrial sheath of mature spermatozoa. Taken together, our results suggest that Tep22 is involved in the biogenesis of the acrosome as well as in the function of the midpiece of murine spermatozoa.

Acrosome↗
PubMed2003

Subunits of the chaperonin CCT are associated with Tetrahymena microtubule structures and are involved in cilia biogenesis.

The cytosolic chaperonin CCT is a heterooligomeric complex of about 900 kDa that mediates the folding of cytoskeletal proteins. We observed by indirect immunofluorescence that the Tetrahymena TpCCTalpha, TpCCTdelta, TpCCTepsilon, and TpCCTeta-subunits colocalize with tubulin in cilia, basal bodies, oral apparatus, and contractile vacuole pores. TpCCT-subunits localization was affected during reciliation. These findings combined with atomic force microscopy measurements in reciliating cells indicate that these proteins play a role during cilia biogenesis related to microtubule nucleation, tubulin transport, and/or axoneme assembly. The TpCCT-subunits were also found to be associated with cortex and cytoplasmic microtubules suggesting that they can act as microtubule-associated proteins. The TpCCTdelta being the only subunit found associated with the macronuclear envelope indicates that it has functions outside of the 900 kDa complex. Tetrahymena cytoplasm contains granular/globular-structures of TpCCT-subunits in close association with microtubule arrays. Studies of reciliation and with cycloheximide suggest that these structures may be sites of translation and folding. Combined biochemical techniques revealed that reciliation affects the oligomeric state of TpCCT-subunits being tubulin preferentially associated with smaller CCT oligomeric species in early stages of reciliation. Collectively, these findings indicate that the oligomeric state of CCT-subunits reflects the translation capacity of the cell and microtubules integrity.

Animals↗
PubMed2002

Impaired maturation of the siderophore pyoverdine chromophore in Pseudomonas fluorescens ATCC 17400 deficient for the cytochrome c biogenesis protein CcmC.

Pyoverdines are the main siderophores of fluorescent pseudomonads. They comprise a quinoline chromophore, a peptide chain, and a dicarboxylic acid or a dicarboxylic acid amide side chain. Each Pseudomonas species produces a pyoverdine with a different peptide chain. A cytochrome c biogenesis DeltaccmC mutant of Pseudomonas fluorescens ATCC 17400 produces multiple pyoverdine forms, showing differences at the level of the chromophore or the side chain. When grown in the presence of L-cysteine, DeltaccmC produces only ferribactin, a non-fluorescent precursor of pyoverdine, while addition of oxidized glutathione improves pyoverdine production. We suggest that the conversion of ferribactin to pyoverdine does not take place in the DeltaccmC mutant because of lack of oxidizing power in the periplasm.

Bacterial Proteins↗
PubMed2003

DmsD is required for the biogenesis of DMSO reductase in Escherichia coli but not for the interaction of the DmsA signal peptide with the Tat apparatus.

The DmsD protein is essential for the biogenesis of DMSO reductase in Escherichia coli, and binds the signal peptide of the DmsA subunit, a Tat substrate. This suggests a role as a guidance factor to target pre-DmsA to the translocase. Here, we have analysed the export of fusion proteins in which the DmsA and TorA signal peptides are fused to green fluorescent protein. Both chimeras are efficiently exported to the periplasm in wild-type E. coli cells and we show that their export efficiencies are essentially identical in a mutant lacking DmsD. An authentic Tat substrate, TMAO reductase, is also efficiently exported in the dmsD mutant. The data indicate that DmsD carries out a critical role in DMSO reductase biogenesis/assembly but is not required for the functioning of the DmsA signal peptide.

Carrier Proteins↗
PubMed2003

Involvement of caveolin-2 in caveolar biogenesis in MDCK cells.

Caveolins have been identified as key components of caveolae, specialized cholesterol-enriched raft domains visible as small flask-shaped invaginations of the plasma membrane. In polarized MDCK cells caveolin-1 and -2 are found together on basolateral caveolae whereas the apical membrane, where only caveolin-1 is present, lacks caveolae. Expression of a caveolin mutant prevented the formation of the large caveolin-1/-2 hetero-oligomeric complexes, and led to intracellular retention of caveolin-2 and disappearance of caveolae from the basolateral membrane. Correspondingly, in MDCK cells over-expressing caveolin-2 the basolateral membrane exhibited an increased number of caveolae. These results indicate the involvement of caveolin-2 in caveolar biogenesis.

Animals↗
PubMed2003

Motif CXCC in nitrile hydratase activator is critical for NHase biogenesis in vivo.

Nitrile hydratase (NHase) activator from Rhodococcus sp. N-771 is required for NHase functional expression. The motif 73CXCC76 in the NHase activator sequence was here revealed to be vital for its function by site-directed mutagenesis. All three substitutions of the cysteines by serines resulted in a much lower level of expression of active NHase. Furthermore, interaction between NHase activator and NHase was detected and the critical role of NHase activator was not exhibited in the cysteine oxidization process of NHase. These findings suggest NHase activator mainly participates in iron trafficking in NHase biogenesis as an iron type metallochaperone.

Amino Acid Motifs↗
PubMed1996

Arrest of mitochondrial biogenesis in copper-treated sycamore cells.

Sycamore suspension cells (Acer pseudoplatanus L.) were grown in the presence of sublethal concentrations of copper (50 microM). During the first 5-6 days of treatment, growth was not affected, but cell respiration (coupled and uncoupled) declined to approximately 60% of its normal value. This decline of respiration was attributed to a progressive diminution of the number of mitochondria in copper-treated cells, based on the demonstration of the concomitant decline of (1) cardiolipin (diphosphatidylglycerol) and cytochrome aa3 (cytochrome oxidase), two specific markers of mitochondrial inner membrane, and (2) fumarase activity, a specific marker of mitochondrial matrix space. In addition, the mitochondria extracted from copper-treated cells presented the same properties as those from control cells, concerning substrate oxidation, cardiolipin and cytochrome aa3 contents, and fumarase activity. These results strongly suggest that copper triggered an arrest of mitochondrial biogenesis, which preceded cell division arrest.

Cardiolipins↗
PubMed1997

Biogenesis of Candida albicans Can1 permease expressed in Saccharomyces cerevisiae.

The Candida albicans CAN1 gene, encoding a high-affinity permease for arginine, lysine and histidine, was tagged at its C-terminus with a c-myc epitope and introduced into strains of Saccharomyces cerevisiae lacking basic amino acid permeases. The expression levels of Ca-Can1p were influenced by the available nitrogen source, being almost negligible when cells were grown in the presence of ammonia. Ca-Can1p was shown to follow the secretory pathway in S. cerevisiae. Ca-Can1p activity was not detected in a secretion-defective sec1-1 mutant grown at a non-permissive temperature. Shr3p, an ER protein that participates in the biogenesis of amino acid permeases was also required for the functional expression of Ca-Can1p. The shr3 mutation does not affect the affinity for substrate but does decrease the number of Can1p molecules reaching the plasma membrane.

Amino Acid Transport Systems↗
PubMed1997

Biogenesis of COPI-coated transport vesicles.

Biosynthetic protein transport and sorting along the secretory pathway represents the last step in biosynthesis of a variety of proteins. Proteins destined for delivery to the cell surface are inserted cotranslationally into the endoplasmic reticulum (ER) and, after their correct folding, are transported out of the ER towards their final destinations. The successive compartments of the secretory pathway are connected by vesicular shuttles that mediate delivery of cargo. The formation of these carrier vesicles depends on the recruitment of cytosolic coat proteins that are thought to act as a mechanical device to shape a flattened donor membrane into a spherical vesicle. A general molecular machinery that mediates targeting and fusion of carrier vesicles has also been identified. This review is focused on COPI-coated vesicles that operate in protein transport within the early secretory pathway. Rather than representing a general overview of the role of COPI-coated vesicles, this mini-review will discuss mechanisms specifically related to the biogenesis of COPI-coated vesicles: (i) a possible role of phospholipase D in the formation of COPI-coated vesicles, (ii) a functional role of a novel family of transmembrane proteins, the p24 family, in the initiation of COPI assembly, and (iii) the direction COPI-coated vesicles may take within the early secretory pathway.

Animals↗
PubMed2002

Biogenesis of iron-sulphur clusters in amitochondriate and apicomplexan protists.

During the last 4 years there has been an enormous interest in the question how iron-sulphur ([Fe-S]) clusters, which are essential building blocks for life, are synthesised and assembled into apo-proteins, both in prokaryotes and in eukaryotes. The emerging picture is that the basic mechanism of this pathway has been well conserved during evolution. In yeast and probably all other eukaryotes the mitochondrion is the place where [Fe-S] clusters are synthesised, even for extramitochondrial [Fe-S] cluster-containing proteins, and a number of proteins have been functionally characterised to a certain extent within this pathway. However, almost nothing is known about this aspect in parasitic protists, although recent studies of amitochondriate protists and on the plastid-like organelle of apicomplexan parasites, the apicoplast, have started to change this. In this article I will summarise the current view of [Fe-S] cluster biogenesis in eukaryotes and discuss its implications for amitochondriate protists and for the plastid-like organelle of apicomplexan parasites.

Animals↗
PubMed2006

Fibrillins: from biogenesis of microfibrils to signaling functions.

Fibrillins are large proteins that form extracellular microfibril suprastructures ubiquitously found in elastic and nonelastic tissues. Mutations in fibrillin-1 and -2 lead to a number of heritable connective tissue disorders generally termed fibrillinopathies. Clinical symptoms in fibrillinopathies manifest in the skeletal, ocular, and cardiovascular systems and highlight the importance of fibrillins in development and homeostasis of tissues and organs, including blood vessels, bone, and eye. Microfibrils appear to have dual roles in (1) conferring mechanical stability and limited elasticity to tissues, and (2) modulating the activity of growth factors of the transforming growth factor beta (TGF-beta) superfamily. This chapter's focus is on the biogenesis of microfibrils, developmental expression patterns of fibrillins, signaling functions of microfibrils, and mouse models deficient in fibrillins.

Animals↗