FEBS Letters
FEBS Letters RSS feed. FEBS Letters is one of the world's leading journals in biochemistry and is renowned both for its quality of content and speed of production. Bringing together the most important developments in the molecular biosciences, FEBS Letters provides an international forum for Minireviews, hypotheses and research letters that merit urgent publication.FEBS Letters offers:• Faster publication: − Accepted articles are published online in 3 days − The print version of the article is published in 3 to 5 weeks after acceptance• Full-text article disclosure in HTML and PDF formats• Articles in Press are included in PubMed• Easy online manuscript submission system• Transparent online peer review and manuscript tracking system• No page charges• Free color figures Subject Coverage:The subject area of FEBS Letters is broad. It covers biochemistry (including protein chemistry, enzymology, nucleic acid chemistry, metabolism, and immunochemistry), structural biology, biophysics, computational biology (genomics, proteomics, bioinformatics), molecular genetics, molecular biology and molecular cell biology (signal transduction, intracellular traffic, regulation of cellular proliferation, cell-cell interactions) and systems biology. Studies on microbes, plants and animals at the molecular level are within the scope of FEBS Letters.Submitting Authors: Manuscripts can be submitted to FEBS Letters at: http://ees.elsevier.com/febsletters/
Updated: 8 years 20 weeks ago
Increased miR-374b promotes cell proliferation and the production of aberrant glycosylated IgA1 in B cells of IgA nephropathy
IgA nephropathy (IgAN), one of the most common forms of glomerulonephritis in the world, is characterized by the mesangial deposition of polymeric IgA1 within the kidney [1–3]. Increased percentages of B lymphocytes were noticed and especially in patients with increased concentration of immunoglobulin A in serum [4]. Phosphatase and tensin homolog (PTEN) inhibits phosphoinositide-3-kinase pathway by dephosphorylating PIP3 and prevents Akt activation [5]. Loss of PTEN in B cells of IgAN was evident in the array analysis conducted by Cox et al.
Roles of LIM kinases in central nervous system function and dysfunction
LIM kinase 1 (LIMK1) and LIM kinase 2 (LIMK2) regulate actin dynamics by phosphorylating cofilin. In this review, we outline studies that have shown an involvement of LIMKs in neuronal function and we detail some of the pathways and molecular mechanisms involving LIMKs in neurodevelopment and synaptic plasticity. We also review the involvement of LIMKs in neuronal diseases and emphasize the differences in the regulation of LIMKs expression and mode of action.We finally present the existence of a cofilin-independent pathway also involved in neuronal function.
PKCβII inhibits the ubiquitination of β-arrestin2 in an autophosphorylation-dependent manner
The desensitization of G protein-coupled receptors (GPCRs) was originally defined as a diminishment in receptor responsiveness through receptor phosphorylation by second messenger-dependent protein kinases, such as protein kinases A and C (PKA and PKC) [1–3]. PKA and PKC can phosphorylate both agonist-occupied and unoccupied GPCRs without discrimination (heterologous). Later, a universal mechanism for desensitizing GPCRs was proposed (homologous, agonist-induced). Homologous desensitization is known to be mediated by the coordinated actions of two families of proteins, the G protein-coupled receptor serine/threonine kinases (GRKs) and the arrestins [4–6].
Membrane insertion and topology of the amino-terminal domain TMD0 of multidrug-resistance associated protein 6 (MRP6)
ATP-binding cassette (ABC) transporters constitute a superfamily of proteins that transport a wide variety of substances across biological membranes by using ATP hydrolysis as an energy source [1]. These transporters consist of a core structure typically containing two transmembrane domains (TMD1 and TMD2) and two nucleotide-binding domains (NBD1 and NBD2). One of the 48 human members of this superfamily is the multidrug-resistance associated protein 6 (MRP6, ABCC6), which physiological function and substrates are unknown.
secreted Pro-Pro endopeptidase PPEP-1 (ZMP1/CD2830) modulates adhesion through cleavage of the collagen binding protein CD2831
Once a pathogenic bacterium enters a host it uses an arsenal of proteins, secreted or displayed on the cell surface, that may fend off host defence mechanisms, breach physical barriers, allow colonization or cause cell death. In addition to toxins, that have a direct deleterious effect on the host, bacteria also secrete proteases to perform ‘housekeeping’ functions such as signalling, attachment, and providing nutrients [1]. Some extracellular proteases are involved in interspecies competition by lysing cell walls of other bacteria [2,3].
Activation of muscarinic cholinoceptor ameliorates tumor necrosis factor-α-induced barrier dysfunction in intestinal epithelial cells
Intestinal epithelial cells (IECs) functions, as a barrier to restrict the passage of pathogenic antigens into the interstitium. Disruption of intestinal barrier integrity may lead to the penetration of luminal bacterial products into the submucosa to trigger local inflammation [1]. Barrier dysfunction is one of the main indicators of the inflammatory bowel diseases (IBD). Therefore, modulation of the epithelial barrier function is currently viewed as a potentially positive pharmacological outcome.
JNK1 inhibits transcriptional and pro-apoptotic activity of TAp63γ
c-Jun N-terminal kinase 1 (JNK1), also known as stress-activated protein kinase 1 (SAPK1), belongs to the mitogen activated protein kinase (MAPK) family [1]. JNK1 can be activated by a variety of environmental stress including DNA damage, heat shock and pro-inflammatory cytokines [2–4]. In these cases, JNK1 is phosphorylated at Thr183 and Tyr185 sites by MKK4 or MKK7 kinases and becomes activated [5]. Activated JNK1 translocates from cytoplasm to nucleus where it phosphorylates multiple transcription factors, including primarily components of AP-1 such as c-Jun and ATF2, thus regulating AP-1 transcriptional activity [6].
Low-temperature microRNA expression in the painted turtle, during freezing stress
For a number of ectothermic animals, freeze tolerance is a strategy of winter survival in subzero temperatures. In these animals, a number of biochemical and cellular changes take place to permit the freezing of extracellular body fluids. Since the first report in 1988, a number of studies have documented the freezing of some species of hatchling turtles while overwintering in the natal nests [32]. Painted turtles (Chrysemys picta) hatch from their eggs in late summer, but do not emerge from their nest until the following spring.
Michael addition of dehydroalanine-containing MAPK peptides to catalytic lysine inhibits the activity of phosphothreonine lyase
The OspF protein family comprises type III effectors that are conserved in both plant and animal bacterial pathogens. The family members include OspF from Shigella, SpvC from Salmonella, and HopAI1 from the plant pathogen Pseudomonas syringae [1]. All of the effectors in the family are phosphothreonine lyases that specifically target host MAPKs [the extracellular signal-regulated kinases (Erk) p38 in mammals and MPK3/4/6 in plants] and inactivate host signaling pathways [1–5]. MAPKs are activated by dual phosphorylation of a conserved Thr-X-Tyr motif in their activation loops [6].
Kinetic analysis of gluconate phosphorylation by human gluconokinase using isothermal titration calorimetry
Gluconate (Glcn) is a naturally occurring carboxylic acid that is found abundantly in various fruits, vegetables and dairy products as well as being added to processed foods and pharmaceuticals due to its refreshing taste. Gluconate has also found use in formulation chemistry, both in industry and in the health sector on account of its metal chelating properties. In the clinic, calcium gluconate is used for treating calcium deficiency, hydrofluoric acid burns and as dietary supplements in the form of zinc gluconate and iron gluconate derivatives [1,2].
Bent out of shape: α-Synuclein misfolding and the convergence of pathogenic pathways in Parkinson’s disease
Protein inclusions made up primarily of misfolded α-synuclein (α-Syn) are the hallmark of a set of disorders known as synucleinopathies, most notably Parkinson’s disease (PD). It is becoming increasingly appreciated that α-Syn misfolding can spread to anatomically connected regions in a prion-like manner. The protein aggregates that ensue are correlated with neurodegeneration in the various yet select neuronal populations that are affected. Recent advances have begun to shed light on the spreading and toxicity mechanisms that may be occurring in PD.
Molecular heterogeneity of midbrain dopaminergic neurons – Moving toward single cell resolution
Since their discovery, midbrain dopamine (DA) neurons have been researched extensively, in part because of their diverse functions and involvement in various neuropsychiatric disorders. Over the last few decades, reports have emerged that midbrain DA neurons were not a homogeneous group, but that DA neurons located in distinct anatomical locations within the midbrain had distinctive properties in terms of physiology, function, and vulnerability. Accordingly, several studies focused on identifying heterogeneous gene expression across DA neuron clusters.
Understanding the susceptibility of dopamine neurons to mitochondrial stressors in Parkinson’s disease
Mitochondria are undoubtedly changed in Parkinson’s disease (PD), and mitochondrial functions are disrupted in genetic and pharmacologic models of PD. However, many of these changes might not truly drive neurodegeneration. PD is defined by the particular susceptibility of nigrostriatal dopamine (DA) neurons, but little is understood about the mitochondria in these cells. Here, we critically review the evidence that mitochondrial stressors cause PD. We then consider how changes in the intrinsic function of mitochondria and in their mass, distribution, and dynamics might synergize with an increased need for mitochondria and produce PD, and the importance of understanding how mitochondria contribute to its pathogenesis.
Cell fate determination, neuronal maintenance and disease state: The emerging role of transcription factors Lmx1a and Lmx1b
LIM-homeodomain (LIM-HD) proteins are evolutionary conserved developmental transcription factors. LIM-HD Lmx1a and Lmx1b orchestrate complex temporal and spatial gene expression of the dopaminergic pathway, and evidence shows they are also involved in adult neuronal homeostasis. In this review, the multiple roles played by Lmx1a and Lmx1b will be discussed. Controlled Lmx1a and Lmx1b expression and activities ensure the proper formation of critical signaling centers, including the embryonic ventral mesencephalon floor plate and sharp boundaries between lineage-specific cells.
Caspase-3 cleaved p65 fragment dampens NF-κB-mediated anti-apoptotic transcription by interfering with the p65/RPS3 interaction
The nuclear factor-kappa B (NF-κB) signaling pathway is pivotal for a wide array of cellular processes [1–5]. Albeit the signaling cascade that leads to NF-κB activation has been extensively studied [6–11], it remains elusive how NF-κB specifically activates its target genes [12–15]. Ribosomal protein S3 (RPS3) was identified as an essential component in NF-κB complexes where RPS3 can interact with the NF-κB p65 subunit in the cytoplasm and the nucleus [16]. The subcellular localization of RPS3 is precisely regulated by the NF-κB activation signaling cascade, in particular the Inhibitor of κB (IκB) kinase beta (IKKβ)-mediated phosphorylation of RPS3 at serine 209 (Ser209) plays an important role for the nuclear translocation and function of RPS3 [17].
PIP1 aquaporins: Intrinsic water channels or PIP2 aquaporin modulators?
The highly conserved plant aquaporins, known as Plasma membrane Intrinsic Proteins (PIPs), are the main gateways for cell membrane water exchange. Years of research have described in detail the properties of the PIP2 subfamily. However, characterizing the PIP1 subfamily has been difficult due to the failure to localize to the plasma membrane. In addition, the discovery of the PIP1–PIP2 interaction suggested that PIP1 aquaporins could be regulated by a complex posttranslational mechanism that involves trafficking, heteromerization and fine-tuning of channel activity.
Co-silencing of human Bub3 and dynein highlights an antagonistic relationship in regulating kinetochore–microtubule attachments
Faithful chromosome segregation in mitosis relies on appropriate kinetochore–microtubule (KT-MT) attachments, under the surveillance of the spindle assembly checkpoint (SAC). The SAC prevents anaphase onset until all chromosomes accomplish proper bipolar attachments and come under tension. Core components of the SAC proteins include, among others, the evolutionary conserved Mad2, Bub3, and BubR1, which form the mitotic checkpoint complex (MCC) with Cdc20 whenever unattached or improperly attached kinetochores are present.
The closed conformation of the LDL receptor is destabilized by the low Ca concentration but favored by the high Mg concentration in the endosome
The low density lipoproteins (LDL) receptor (LDLR) plays a key role in internalization of LDL and VLDL remnants in the liver and peripheral tissues [1,2]. The LDLR binds circulating LDL and VLDL particles, and is internalized in endosomes where the cargo lipoprotein is released for degradation in lyzosomes, while the receptor is recycled to the cell surface. Defects in the LDLR function result in elevated concentrations of circulating cholesterol and are the major cause of familial hypercholesterolemia (FH) [3–5].
Profiling metabolic remodeling in PP2Acα deficiency and chronic pressure overload mouse hearts
In metazoans, the constant generation of ATP is vital for the heart to maintain its pump function. Therefore, cardiomyocytes must be able to dynamically re-program fuel and energize their metabolic capacity in response to environmental and physiological cues to ensure that energy supply meets demands. During the early stages of heart development, remodeling the fetal into the adult heart is a complicated process, which relies on important transitions that are triggered shortly after birth [1,2].