Quinones in plant plasma membranes — a missing link?

Summary The occurrence of a vitamin-K-like substance (naphthoquinone group) and flavins (flavin mononucleotide and flavin adenine dinucleotide) is demonstrated in plasma membranes isolated from maize (Zea mays L.) roots, on the basis of high-pressure liquid chromotography and spectral analysis. At least three NAD(P)H dehydrogenases could be purified to homogeneity from this plant material. Two of these proteins (25 and 30 kDa) reduce hexacyanoferrate III and quinones, while the third (41 kDa) reduces oxalacetic acid but not hexacyanoferrate III in the presence of NADH. Low-temperature spectra demonstrate the occurrence of a b-type cytochrome in plasma membranes isolated from maize roots. The latter compound could be reduced by ascorbic acid (E₀ > +80 mV) and shows an -band maximum at 559 nm (at –196 °C). NADH-dependent cytochromeb reduction could be observed only in the presence of detergent and increased after preincubation with vitamin K₃ (menadione). On the basis of the presented data a possible function of naphthoquinones in plasma membrane electron transfer is discussed.Abbreviations Brij 58 polyoxyethylene 20 cetyl ether - Coenzyme Q₁₀ ubiquinone-50 - duroquinone tetramethyl-p-benzoquinone - E₀ standard redox potential - Na₂EDTA ethylenediaminetetraacetic acid disodium salt - HEPES N-[2-hydroxyethyl]piperazine-N[2-ethane-sulfonic acid] - juglone 5-hydroxy-1,4-naphthoquinone - PMSF phenylmethylsulfonyl fluoride - vitamin K₁ 2-methyl-3-phyty 1-1,4-naphthoquinone - vitamin K₃ 2-methyl-1,4-naphthoquinone     

The search for the missing link: a relic plastid in Perkinsus?

Perkinsus marinus (Phylum Perkinsozoa) is a protozoan parasite that has devastated natural and farmed oyster populations in the USA, significantly affecting the shellfish industry and the estuarine environment. The other two genera in the phylum, Parvilucifera and Rastrimonas, are parasites of microeukaryotes. The Perkinsozoa occupies a key position at the base of the dinoflagellate branch, close to its divergence from the Apicomplexa, a clade that includes parasitic protista, many harbouring a relic plastid. Thus, as a taxon that has also evolved toward parasitism, the Perkinsozoa has attracted the attention of biologists interested in the evolution of this organelle, both in its ultrastructure and the conservation, loss or transfer of its genes. A review of the recent literature reveals mounting evidence in support of the presence of a relic plastid in P. marinus, including the presence of multimembrane structures, characteristic metabolic pathways and proteins with a bipartite N-terminal extension. Further, these findings raise intriguing questions regarding the potential functions and unique adaptation of the putative plastid and/or plastid genes in the Perkinsozoa. In this review we analyse the above-mentioned evidence and evaluate the potential future directions and expected benefits of addressing such questions. Given the rapidly expanding molecular/genetic resources and methodological toolbox for Perkinsus spp., these organisms should complement the currently established models for investigating plastid evolution within the Chromalveolata.     

Cell polarity: The missing link in skeletal morphogenesis?

Despite extensive genetic analysis of the dynamic multi-phase process that transforms a small population of lateral plate mesoderm into the mature limb skeleton, the mechanisms by which signaling pathways regulate cellular behaviors to generate morphogenetic forces are not known. Recently, a series of papers have offered the intriguing possibility that regulated cell polarity fine-tunes the morphogenetic process via orienting cell axes, division planes and cell movements. Wnt5a-mediated non-canonical signaling, which may include planar cell polarity, has emerged as a common thread in the otherwise distinct signaling networks that regulate morphogenesis in each phase of limb development. These findings position the limb as a key model to elucidate how global tissue patterning pathways direct local differences in cell behavior that, in turn, generate growth and form.     

CFTR: a missing link between exocrine and endocrine pancreas?

<正>Cystic fibrosis(CF),a life-shortening hereditary disease mainly afflicting people of Caucasian origins,is caused by loss-of-function mutations in the CFTR(Cystic Fibrosis Transmembrane conductance Regulator)gene,which encodes a phosphorylation-activated,but ATP-gated anion channel expressed primarily in epithelial cells.To date,nearly 2000 mutations have been identified as pathogenic,     

Innate immunity: the missing link in neuroprotection and neurodegeneration?

Innate immunity was previously thought to be a nonspecific immunological programme that was engaged by peripheral organs to maintain homeostasis after stress and injury. Emerging evidence indicates that this highly organized response also takes place in the central nervous system. Through the recognition of neuronal fingerprints, the long-term induction of the innate immune response and its transition to an adaptive form might be central to the pathophysiology and aetiology of neurodegenerative disorders. Paradoxically, this response also protects neurons by favouring remyelination and trophic support afforded by glial cells.     

The missing link(er): a return to symmetry in antigen receptor signaling?

B lymphocytes and T lymphocytes utilize several proteins with common functions to transduce signals from their respective receptors. However, at the hierarchial signalling level of SLP-76 [Src homology 2(SH2) domain-containing leukocyte protein of 76-kDa] and LAT (linker for activation of T cells) in T cells, the only corresponding protein in B cells was known to be BLNK (B cell linker protein). It was thought that perhaps BLNK performed the cognate roles of SLP-76 and LAT in B cells; however, mounting evidence to the contrary revealed that this hypothesis was not robust. Two laboratories have recently described the characterization of a protein expressed in B cells and myeloid cells, alternatively termed NTAL (non-T cell activation linker) or LAB (linker for activation of B cells). NTAL/LAB and LAT may have arisen from a primordial gene-duplicating event, but genes that code for the two proteins do not share a very high degree of sequence identity. Wange discusses the results of the two reports, the evidence for functional homology between LAT and NTAL/LAB, and the possibility that the differences between them might lead to specific clinical therapeutics to manipulate immune cell responses.     

G-quadruplexes within prion mRNA: the missing link in prion disease?

Cellular ribonucleic acid (RNA) plays a crucial role in the initial conversion of cellular prion protein PrP^C to infectious PrP^Sc or scrapie. The nature of this RNA remains elusive. Previously, RNA aptamers against PrP^C have been isolated and found to form G-quadruplexes (G4s). PrP^C binding to G4 RNAs destabilizes its structure and is thought to trigger its conversion to PrP^Sc. Here it is shown that PrP messenger RNA (mRNA) itself contains several G4 motifs, located in the octarepeat region. Investigation of the RNA structure in one of these repeats by circular dichroism, nuclear magnetic resonance and ultraviolet melting studies shows evidence of G4 formation. In vitro translation of full-length PrP mRNA, naturally harboring five consecutive G4 motifs, was specifically affected by G4-binding ligands, lending support to G4 formation in PrP mRNA. A possible role of PrP binding to its own mRNA and the role of anti-prion drugs, many of which are G4-binding ligands, in prion disease are discussed.     

Calcium influx: is Homer the missing link?

Calcium signals in cells can arise via release from intracellular stores or influx across the plasma membrane. Recent studies have shed new light on the multi-protein signalling complexes that mediate communication between calcium stores and plasma membrane calcium channels.     

Actin and microtubules in neurite initiation: are MAPs the missing link?

During neurite initiation microtubules align to form a tight bundle and actin filaments reorganize to produce a growth cone. The mechanisms that underlie these highly coordinated cytoskeletal rearrangements are not yet fully understood. Recently, various levels of coordination between the actin- and microtubule-based cytoskeletons have been observed during cellular migration and morphogenesis, processes that share some similarities to neurite initiation. Direct, physical association between both cytoskeletons has been suggested, because microtubules often preferentially grow along actin bundles and transiently target actin-rich adhesion complexes. We propose that such physical association might be involved in force-based interactions and spatial organization of the two networks during neurite initiation as well. In addition, many signaling cascades that affect actin filaments are also involved in the regulation of microtubule dynamics, and vice versa. Although several candidates for mediating these effects have been identified in non-neuronal cells, the general mechanism is still poorly understood. In neurons certain plakins and neuron-specific microtubule associated proteins (MAPs), like MAP1B and MAP2, which can bind to both microtubules and F-actin, are promising candidates to play key roles in the specific cytoskeletal rearrangements controlling the transition from an undifferentiated state to neurite-bearing morphology. Here we review the effects of MAPs on microtubules and actin, as well as the coordination of both cytoskeletons during neurite initiation.     

Toll-like receptor signalling in liver disease: ER stress the missing link?

Toll-like receptors induce a complex inflammatory response that can function to alert the body to infection, neutralize pathogens and repair damaged tissues. Toll-like receptors are expressed on kupffer, endothelial, dendritic, biliary epithelial, hepatic stellate cells, and hepatocytes in the liver. The endoplasmic reticulum (ER) is a central organelle of eukaryotic cells that exists as a place of lipid synthesis, protein folding and protein maturation. The ER is a major signal transduction organelle that senses and responds to changes in homeostasis. Conditions interfering with the function of the ER are collectively known as ER stress and can be induced by accumulation of unfolded protein aggregates or by excessive protein traffic as can occur during viral infection. The ability of ER stress to induce an inflammatory response is considered to play a role in disease pathogenesis. Importantly, ER stress is viewed as a contributor to the pathogenesis of liver diseases with evidence linking components of ER homeostasis as requirements for optimal Toll-like receptor function. In this context this review discusses the association of Toll-like receptors with ER stress. This is an emerging paradigm in the understanding of Toll-like receptor signalling which may have an underlying role in the pathogenesis of liver disease.