An RNA exosome subunit mediates cell-to-cell trafficking of a homeobox mRNA via plasmodesmata

mRNA migration through plasmodesmata In plants, certain transcription factors are produced in one cell but transported, sometimes as messenger RNA (mRNA), through plasmodesmata, channels between neighboring plant cells, where they act. This system helps to manage stem cell development. Kitagawa et al . now identify part of the machinery that manages this cell-to-cell transport. Transport of the mRNA encoding the KNOTTED1 homeobox transcription factor depends on Ribosomal RNA-Processing Protein 44 (AtRRP44A), which is a subunit of the RNA exosome. —PJH

The Role of Cell Membranes in Cell Traffic

The cell membrane plays an important role in cell traffic because it functions to secrete various molecules. The selective transport system allows the movement of molecules into or out of the cell compartment. By controlling the movement of substances from one compartment to another, membranes exert a strong influence on metabolic pathways. Cell membranes are composed of proteins and lipids with a very important function in maintaining the rhythm of circulation and cell transport. In addition, the cell membrane also plays a role in maintaining the integrity and relationship, and communication of cells.

Efficient transport and biotransformation of dipeptide-like tyrosine/phenylalanine-conjugated phenolic amide esters in THP-1 cells and PBMCs: A potential means for transporting compounds inside monocytes/macrophages

Background: Recent studies suggest that dipeptide-like tyrosine/phenylalanine-conjugated phenolic amide compounds may contain several biological activities including anti-inflammatory activity. However, there is currently no information about their transport and biotransformation in monocytes/macrophages involved in inflammation process. Objective: The objective of this study was to investigate cell transport and biotransformation of the phenolic amides and esters in monocyte/macrophage-like cells. Methods: Cell transport and biotransformation of the phenolic amides and esters (N-coumaroylphenylalanine, N-caffeoylphenylalanine, N-feruloylphenylalanine, N-coumaroyltyrosine, N-caffeoyltyrosine, N-feruloyltyrosine and their O-methyl esters) were investigated in THP-1 cells and PBMCs using HPLC, cellular and kinetics methods Results: In THP-1 cells, the phenolic amides were not transported significantly, but their O-methyl esters were transported significantly (P < 0.02). Also, the transport of the esters was found to be sodium-independent and pH-dependent. Among the tested esters, N-feruloylphenylalanine-O-methyl ester showed the highest uptake (Km of 25 µM), and the uptake was inhibited by PepT1/2 substrate and blocker (GlySar and enalapril) in THP-1 cells. Particularly, enalapril competitively inhibited the uptake with Ki of 560 µM. The data also showed that N-feruloylphenylalanine-O-methyl ester and N-feruloyltyrosine-O-methyl ester could be biotransformed into parent phenolic amides in THP-1 cells. Similarly, the ester compounds were also found to be transported and biotransformed in PBMCs. Conclusion: The data suggest that dipeptide-like tyrosine/phenylalanine-conjugated phenolic amide esters may be transported and biotransformed in THP-1 cells and PBMCs.

Spontaneous Mutation in the Movement Protein of Citrus Leprosis Virus C2, in a Heterologous Virus Infection Context, Increases Cell-to-Cell Transport and Generates Fitness Advantage

Previous results using a movement defective alfalfa mosaic virus (AMV) vector revealed that citrus leprosis virus C (CiLV-C) movement protein (MP) generates a more efficient local movement, but not more systemic transport, than citrus leprosis virus C2 (CiLV-C2) MP, MPs belonging to two important viruses for the citrus industry. Here, competition experiment assays in transgenic tobacco plants (P12) between transcripts of AMV constructs expressing the cilevirus MPs, followed by several biological passages, showed the prevalence of the AMV construct carrying the CiLV-C2 MP. The analysis of AMV RNA 3 progeny recovered from P12 plant at the second viral passage revealed the presence of a mix of progeny encompassing the CiLV-C2 MP wild type (MPWT) and two variants carrying serines instead phenylalanines at positions 72 (MPS72F) or 259 (MPS259F), respectively. We evaluated the effects of each modified residue in virus replication, and cell-to-cell and long-distance movements. Results indicated that phenylalanine at position 259 favors viral cell-to-cell transport with an improvement in viral fitness, but has no effect on viral replication, whereas mutation at position 72 (MPS72F) has a penalty in the viral fitness. Our findings indicate that the prevalence of a viral population may be correlated with its greater efficiency in cell-to-cell and systemic movements.

Duplication of NRAMP3 gene in poplars generated two homologous transporters with distinct functions

ABSTRACTTransition metals are essential for a wealth of metabolic reactions, but their concentrations need to be tightly controlled across cells and cell compartments, as metal excess or imbalance has deleterious effects. Metal homeostasis is achieved by a combination of metal transport across membranes and metal binding to a variety of molecules. Gene duplication is a key process in evolution, as emergence of advantageous mutations on one of the copies can confer a new function. Here, we report that the poplar genome contains two paralogues encoding NRAMP3 metal transporters localized in tandem. All Populus species analyzed had two copies of NRAMP3, whereas only one could be identified in Salix species indicating that duplication occurred when the two genera separated. Both copies are under purifying selection and encode functional transporters, as shown by expression in the yeast heterologous expression system. However, genetic complementation revealed that only one of the paralogues has retained the original function in release of metals stored in the vacuole previously characterized in A. thaliana. Confocal imaging showed that the other copy has acquired a distinct localization to the Trans Golgi Network (TGN). Expression in poplar indicated that the copy of NRAMP3 localized on the TGN has a novel function in the control of cell-to-cell transport of manganese. This work provides a clear case of neo-functionalization through change in the subcellular localization of a metal transporter as well as evidence for the involvement of the secretory pathway in cell-to-cell transport of manganese.

Microfluidic Cell Transport with Piezoelectric Micro Diaphragm Pumps

The automated transport of cells can enable far-reaching cell culture research. However, to date, such automated transport has been achieved with large pump systems that often come with long fluidic connections and a large power consumption. Improvement is possible with space- and energy-efficient piezoelectric micro diaphragm pumps, though a precondition for a successful use is to enable transport with little to no mechanical stress on the cell suspension. This study evaluates the impact of the microfluidic transport of cells with the piezoelectric micro diaphragm pump developed by our group. It includes the investigation of different actuation signals. Therewith, we aim to achieve optimal fluidic performance while maximizing the cell viability. The investigation of fluidic properties proves a similar performance with a hybrid actuation signal that is a rectangular waveform with sinusoidal flanks, compared to the fluidically optimal rectangular actuation. The comparison of the cell transport with three actuation signals, sinusoidal, rectangular, and hybrid actuation shows that the hybrid actuation causes less damage than the rectangular actuation. With a 5% reduction of the cell viability it causes similar strain to the transport with sinusoidal actuation. Piezoelectric micro diaphragm pumps with the fluidically efficient hybrid signal actuation are therefore an interesting option for integrable microfluidic workflows.

Structure and biological action of analogs and derivatives of biogenic polyamines

Objectives. Biogenic polyamines are widely present in nature. They are characteristic of both protozoan cells and multicellular organisms. These compounds have a wide range of biological functions and are necessary for normal growth and development of cells. Violation of polyamine homeostasis can cause significant abnormalities in cell functioning, provoking various pathological processes, including oncological and neuropsychiatric diseases. The impact on the “polyamine pathway” is an attractive basis for the creation of many pharmacological agents with a diverse spectrum of action. The purpose of this review is to summarize the results of the studies devoted to understanding the biological activity of compounds of the polyamine series, comparing their biological action with action on certain molecular targets. Due to the structural diversity of this group of substances, it is impossible to fully reflect the currently available data in one review. Therefore, in this work, the main attention is paid to the derivatives, acyclic saturated polyamines.Results. The following aspects are considered: biological functionality, biosynthesis and catabolism, cell transport, and localization of biogenic polyamines in the living systems. Structural analogs and derivatives of biogenic polyamines with antitumor, neuroprotective, antiarrhythmic, antiparasitic, antibacterial, and other biological activities are represented; the relationship between biological activity and the target of exposure is reflected. It was found that the nature of the substituent, the number of cationic centers, and the length of the polyamine chain have a great influence on the nature of the effect.Conclusions. At present, the use of polyamine structures is restrained by cytotoxicity and nonspecific toxic effects on the central nervous system. Further research in the field of biochemistry, cell transport, and a deeper understanding of receptor interaction mechanisms will help making polyamines as the basis for potential drug formulation.

Tau and Membranes: Interactions That Promote Folding and Condensation

Tau misfolding and assembly is linked to a number of neurodegenerative diseases collectively described as tauopathies, including Alzheimer’s disease (AD) and Parkinson’s disease. Anionic cellular membranes, such as the cytosolic leaflet of the plasma membrane, are sites that concentrate and neutralize tau, primarily due to electrostatic interactions with tau’s microtubule binding repeat domain (RD). In addition to electrostatic interactions with lipids, tau also has interactions with membrane proteins, which are important for tau’s cellular functions. Tau also interacts with lipid tails to facilitate direct translocation across the membrane and can form stable protein-lipid complexes involved in cell-to-cell transport. Concentrated tau monomers at the membrane surface can form reversible condensates, change secondary structures, and induce oligomers, which may eventually undergo irreversible crosslinking and fibril formation. These β-sheet rich tau structures are capable of disrupting membrane organization and are toxic in cell-based assays. Given the evidence for relevant membrane-based tau assembly, we review the emerging hypothesis that polyanionic membranes may serve as a site for phase-separated tau condensation. Membrane-mediated phase separation may have important implications for regulating tau folding/misfolding, and may be a powerful mechanism to spatially direct tau for native membrane-mediated functions.

Concentration of intraflagellar transport proteins at the ciliary base is required for proper train injection

Construction of cilia and flagella relies on Intraflagellar Transport (IFT). Although IFT proteins can be found in multiple locations in the cell, transport has only been reported along the axoneme. Here, we reveal that IFT concentration at the base of the flagellum of Trypanosoma brucei is required for proper assembly of IFT trains. Using live cell imaging at high resolution and direct optical nanoscopy with axially localized detection (DONALD) of fixed trypanosomes, we demonstrate that IFT proteins are localised around the 9 doublet microtubules of the proximal portion of the transition zone, just on top of the transition fibres. Super-resolution microscopy and photobleaching studies reveal that knockdown of the RP2 transition fibre protein results in reduced IFT protein concentration and turnover at the base of the flagellum. This in turn is accompanied by a 4- to 8-fold drop in the frequency of IFT train injection. We propose that the flagellum base provides a unique environment to assemble IFT trains.