Toxoplasma gondii chromosomal passenger complex is essential for the organization of a functional mitotic spindle: a prerequisite for productive endodyogeny.
Abstract The phylum Apicomplexa encompasses deadly pathogens such as malaria and Cryptosporidium. Apicomplexa cell division is mechanistically divergent from that of their mammalian host, potentially representing an attractive source of drug targets. Depending on the species, apicomplexan parasites can modulate the output of cell division, producing two to thousands of daughter cells at once. The inherent flexibility of their cell division mechanisms allows these parasites to adapt to different niches, facilitating their dissemination. Toxoplasma gondii tachyzoites divide using a unique form of cell division calle...
Source: Cellular and Molecular Life Sciences : CMLS - July 26, 2018 Category: Cytology Authors: Berry L, Chen CT, Francia ME, Guerin A, Graindorge A, Saliou JM, Grandmougin M, Wein S, Bechara C, Morlon-Guyot J, Bordat Y, Gubbels MJ, Lebrun M, Dubremetz JF, Daher W Tags: Cell Mol Life Sci Source Type: research

Non-canonical Wnt signals regulate cytoskeletal remodeling in osteoclasts.
Abstract Osteoclasts are multinucleated cells responsible for bone resorption. Osteoclasts adhere to the bone surface through integrins and polarize to form actin rings, which are formed by the assembly of podosomes. The area contained within actin rings (also called sealing zones) has an acidic pH, which causes dissolution of bone minerals including hydroxyapatite and the degradation of matrix proteins including type I collagen by the protease cathepsin K. Osteoclasts resorb bone matrices while moving on bone surfaces. Osteoclasts change their cell shapes and exhibit three modes for bone resorption: motile resorb...
Source: Cellular and Molecular Life Sciences : CMLS - July 26, 2018 Category: Cytology Authors: Uehara S, Udagawa N, Kobayashi Y Tags: Cell Mol Life Sci Source Type: research

Cellular mechanisms and signals that coordinate plasma membrane repair.
Abstract Plasma membrane forms the barrier between the cytoplasm and the environment. Cells constantly and selectively transport molecules across their plasma membrane without disrupting it. Any disruption in the plasma membrane compromises its selective permeability and is lethal, if not rapidly repaired. There is a growing understanding of the organelles, proteins, lipids, and small molecules that help cells signal and efficiently coordinate plasma membrane repair. This review aims to summarize how these subcellular responses are coordinated and how cellular signals generated due to plasma membrane injury intera...
Source: Cellular and Molecular Life Sciences : CMLS - July 26, 2018 Category: Cytology Authors: Horn A, Jaiswal JK Tags: Cell Mol Life Sci Source Type: research

Bacterial laccases: promising biological green tools for industrial applications.
Abstract Multicopper oxidases (MCOs) are a pervasive family of enzymes that oxidize a wide range of phenolic and nonphenolic aromatic substrates, concomitantly with the reduction of dioxygen to water. MCOs are usually divided into two functional classes: metalloxidases and laccases. Given their broad substrate specificity and eco-friendliness (molecular oxygen from air as is used as the final electron acceptor and they only release water as byproduct), laccases are regarded as promising biological green tools for an array of applications. Among these laccases, those of bacterial origin have attracted research atte...
Source: Cellular and Molecular Life Sciences : CMLS - July 25, 2018 Category: Cytology Authors: Guan ZB, Luo Q, Wang HR, Chen Y, Liao XR Tags: Cell Mol Life Sci Source Type: research

The roles of base excision repair enzyme OGG1 in gene expression.
Abstract Modifications of DNA strands and nucleobases-both induced and accidental-are associated with unfavorable consequences including loss or gain in genetic information and mutations. Therefore, DNA repair proteins have essential roles in keeping genome fidelity. Recently, mounting evidence supports that 8-oxoguanine (8-oxoG), one of the most abundant genomic base modifications generated by reactive oxygen and nitrogen species, along with its cognate repair protein 8-oxoguanine DNA glycosylase1 (OGG1), has distinct roles in gene expression through transcription modulation or signal transduction. Binding to 8-o...
Source: Cellular and Molecular Life Sciences : CMLS - July 24, 2018 Category: Cytology Authors: Wang R, Hao W, Pan L, Boldogh I, Ba X Tags: Cell Mol Life Sci Source Type: research

Viral journeys on the intracellular highways.
We describe broadly required components of the endocytic and secretory pathways, the Endosomal Sorting Complexes Required for Transport pathway, and the autophagy pathway. Identification of such overlapping host functions offers new opportunities to develop broad-spectrum host-targeted antiviral strategies. PMID: 30043139 [PubMed - as supplied by publisher] (Source: Cellular and Molecular Life Sciences : CMLS)
Source: Cellular and Molecular Life Sciences : CMLS - July 24, 2018 Category: Cytology Authors: Robinson M, Schor S, Barouch-Bentov R, Einav S Tags: Cell Mol Life Sci Source Type: research

Melatonin receptors limit dopamine reuptake by regulating dopamine transporter cell-surface exposure.
In conclusion, we reveal one of the first molecular complexes between G protein-coupled receptors (MT1 and MT2) and transporters (DAT) in which melatonin receptors regulate the availability of DAT at the plasma membrane, thus limiting the striatal DA re-uptake capacity in mice. PMID: 30043140 [PubMed - as supplied by publisher] (Source: Cellular and Molecular Life Sciences : CMLS)
Source: Cellular and Molecular Life Sciences : CMLS - July 24, 2018 Category: Cytology Authors: Benleulmi-Chaachoua A, Hegron A, Le Boulch M, Karamitri A, Wierzbicka M, Wong V, Stagljar I, Delagrange P, Ahmad R, Jockers R Tags: Cell Mol Life Sci Source Type: research

Serine protease PRSS55 is crucial for male mouse fertility via affecting sperm migration and sperm-egg binding.
In conclusion, we have demonstrated that PRSS55 plays vital roles in regulating male fertility of mice, including in vivo sperm migration and in vitro sperm-egg interaction, possibly by affecting the maturation of ADAM3 in sperm and the expression of multiple genes in testis. PMID: 30032357 [PubMed - as supplied by publisher] (Source: Cellular and Molecular Life Sciences : CMLS)
Source: Cellular and Molecular Life Sciences : CMLS - July 21, 2018 Category: Cytology Authors: Shang X, Shen C, Liu J, Tang L, Zhang H, Wang Y, Wu W, Chi J, Zhuang H, Fei J, Wang Z Tags: Cell Mol Life Sci Source Type: research

Drosophila Hsp67Bc hot-spot variants alter muscle structure and function.
Abstract The Drosophila Hsp67Bc gene encodes a protein belonging to the small heat-shock protein (sHSP) family, identified as the nearest functional ortholog of human HSPB8. The most prominent activity of sHSPs is preventing the irreversible aggregation of various non-native polypeptides. Moreover, they are involved in processes such as development, aging, maintenance of the cytoskeletal architecture and autophagy. In larval muscles Hsp67Bc localizes to the Z- and A-bands, which suggests its role as part of the conserved chaperone complex required for Z-disk maintenance. In addition, Hsp67Bc is present at neuromus...
Source: Cellular and Molecular Life Sciences : CMLS - July 21, 2018 Category: Cytology Authors: Jabłońska J, Dubińska-Magiera M, Jagla T, Jagla K, Daczewska M Tags: Cell Mol Life Sci Source Type: research

Tryptophan metabolites kynurenine and serotonin regulate fibroblast activation and fibrosis.
Abstract Fibrosis is a pathological form of aberrant tissue repair, the complications of which account for nearly half of all deaths in the industrialized world. All tissues are susceptible to fibrosis under particular pathological sets of conditions. Though each type of fibrosis has characteristics and hallmarks specific to that particular condition, there appear to be common factors underlying fibrotic diseases. One of these ubiquitous factors is the paradigm of the activated myofibroblast in the promotion of fibrotic phenotypes. Recent research has implicated metabolic byproducts of the amino acid tryptophan, n...
Source: Cellular and Molecular Life Sciences : CMLS - July 20, 2018 Category: Cytology Authors: Dolivo DM, Larson SA, Dominko T Tags: Cell Mol Life Sci Source Type: research

Inhibition of protein misfolding and aggregation by natural phenolic compounds.
Abstract Protein misfolding and aggregation into fibrillar deposits is a common feature of a large group of degenerative diseases affecting the central nervous system or peripheral organs, termed protein misfolding disorders (PMDs). Despite their established toxic nature, clinical trials aiming to reduce misfolded aggregates have been unsuccessful in treating or curing PMDs. An interesting possibility for disease intervention is the regular intake of natural food or herbal extracts, which contain active molecules that inhibit aggregation or induce the disassembly of misfolded aggregates. Among natural compounds, p...
Source: Cellular and Molecular Life Sciences : CMLS - July 20, 2018 Category: Cytology Authors: Dhouafli Z, Cuanalo-Contreras K, Hayouni EA, Mays CE, Soto C, Moreno-Gonzalez I Tags: Cell Mol Life Sci Source Type: research

Overview upon miR-21 in lung cancer: focus on NSCLC.
Abstract Considering the high mortality rate encountered in lung cancer, there is a strong need to explore new biomarkers for early diagnosis and also improved therapeutic targets to overcome this issue. The implementation of microRNAs as important regulators in cancer and other pathologies expanded the possibilities of lung cancer management and not only. MiR-21 represents an intensively studied microRNA in many types of cancer, including non-small cell lung cancer (NSCLC). Its role as an oncogene is underlined in multiple studies reporting the upregulated expression of this sequence in patients diagnosed wi...
Source: Cellular and Molecular Life Sciences : CMLS - July 20, 2018 Category: Cytology Authors: Bica-Pop C, Cojocneanu-Petric R, Magdo L, Raduly L, Gulei D, Berindan-Neagoe I Tags: Cell Mol Life Sci Source Type: research

Dysregulation of a novel miR-1825/TBCB/TUBA4A pathway in sporadic and familial ALS.
Abstract Genetic and functional studies suggest diverse pathways being affected in the neurodegenerative disease amyotrophic lateral sclerosis (ALS), while knowledge about converging disease mechanisms is rare. We detected a downregulation of microRNA-1825 in CNS and extra-CNS system organs of both sporadic (sALS) and familial ALS (fALS) patients. Combined transcriptomic and proteomic analysis revealed that reduced levels of microRNA-1825 caused a translational upregulation of tubulin-folding cofactor b (TBCB). Moreover, we found that excess TBCB led to depolymerization and degradation of tubulin alpha-4A (TUBA4A)...
Source: Cellular and Molecular Life Sciences : CMLS - July 20, 2018 Category: Cytology Authors: Helferich AM, Brockmann SJ, Reinders J, Deshpande D, Holzmann K, Brenner D, Andersen PM, Petri S, Thal DR, Michaelis J, Otto M, Just S, Ludolph AC, Danzer KM, Freischmidt A, Weishaupt JH Tags: Cell Mol Life Sci Source Type: research

Cellular senescence: a view throughout organismal life.
Abstract Cellular senescence is the final fate of most cells in response to specific stimuli, but is not the end. Indeed, it is the beginning of a singular life, with multiple side roads leading to diverse effects on the organism. Many studies have been done in the last few years to elucidate the intriguing role of senescent cells in the organism, demonstrating them as the cause of several age-related diseases. However, these cells are also positively implicated in other important pathways, such as embryogenesis and wound healing. It appears that the multiple effects are time-dependent: long-term senescence is mos...
Source: Cellular and Molecular Life Sciences : CMLS - July 20, 2018 Category: Cytology Authors: von Kobbe C Tags: Cell Mol Life Sci Source Type: research

eIF2A, an initiator tRNA carrier refractory to eIF2 α kinases, functions synergistically with eIF5B.
eIF2A, an initiator tRNA carrier refractory to eIF2α kinases, functions synergistically with eIF5B. Cell Mol Life Sci. 2018 Jul 17;: Authors: Kim E, Kim JH, Seo K, Hong KY, An SWA, Kwon J, Lee SV, Jang SK Abstract The initiator tRNA (Met-tRNA iMet ) at the P site of the small ribosomal subunit plays an important role in the recognition of an mRNA start codon. In bacteria, the initiator tRNA carrier, IF2, facilitates the positioning of Met-tRNA iMet on the small ribosomal subunit. Eukarya contain the Met-tRNA iMet carrier, eIF2 (unrelated to IF2), whose carrier activity is inhibited under stress ...
Source: Cellular and Molecular Life Sciences : CMLS - July 17, 2018 Category: Cytology Authors: Kim E, Kim JH, Seo K, Hong KY, An SWA, Kwon J, Lee SV, Jang SK Tags: Cell Mol Life Sci Source Type: research

Targeting epigenetics using synthetic lethality in precision medicine.
Abstract Technological breakthroughs in genomics have had a significant impact on clinical therapy for human diseases, allowing us to use patient genetic differences to guide medical care. The "synthetic lethal approach" leverages on cancer-specific genetic rewiring to deliver a therapeutic regimen that preferentially targets malignant cells while sparing normal cells. The utility of this system is evident in several recent studies, particularly in poor prognosis cancers with loss-of-function mutations that become "treatable" when two otherwise discrete and unrelated genes are targeted simultan...
Source: Cellular and Molecular Life Sciences : CMLS - July 12, 2018 Category: Cytology Authors: Chen ES Tags: Cell Mol Life Sci Source Type: research

The mesenchymoangioblast, mesodermal precursor for mesenchymal and endothelial cells.
Abstract Mesenchymoangioblast (MB) is the earliest precursor for endothelial and mesenchymal cells originating from APLNR+PDGFRα+KDR+ mesoderm in human pluripotent stem cell cultures. MBs are identified based on their capacity to form FGF2-dependent compact spheroid colonies in a serum-free semisolid medium. MBs colonies are composed of PDGFRβ+CD271+EMCN+DLK1+CD73- primitive mesenchymal cells which are generated through endothelial/angioblastic intermediates (cores) formed during first 3-4 days of clonogenic cultures. MB-derived primitive mesenchymal cells have potential to differentiate into mesen...
Source: Cellular and Molecular Life Sciences : CMLS - July 10, 2018 Category: Cytology Authors: Slukvin II, Kumar A Tags: Cell Mol Life Sci Source Type: research

A126 in the active site and TI167/168 in the TI loop are essential determinants of the substrate specificity of PTEN.
Abstract PTEN prevents tumor genesis by antagonizing the PI3 kinase/Akt pathway through D3 site phosphatase activity toward PI(3,4)P2 and PI(3,4,5)P3. The structural determinants of this important specificity remain unknown. Interestingly, PTEN shares remarkable homology to voltage-sensitive phosphatases (VSPs) that dephosphorylate D5 and D3 sites of PI(4,5)P2, PI(3,4)P2, and PI(3,4,5)P3. Since the catalytic center of PTEN and VSPs differ markedly only in TI/gating loop and active site motif, we wondered whether these differences explained the variation of their substrate specificity. Therefore, we introduced muta...
Source: Cellular and Molecular Life Sciences : CMLS - July 9, 2018 Category: Cytology Authors: Leitner MG, Hobiger K, Mavrantoni A, Feuer A, Oberwinkler J, Oliver D, Halaszovich CR Tags: Cell Mol Life Sci Source Type: research

Voltage-gated sodium currents in cerebellar Purkinje neurons: functional and molecular diversity.
Abstract Purkinje neurons, the sole output of the cerebellar cortex, deliver GABA-mediated inhibition to the deep cerebellar nuclei. To subserve this critical function, Purkinje neurons fire repetitively, and at high frequencies, features that have been linked to the unique properties of the voltage-gated sodium (Nav) channels expressed. In addition to the rapidly activating and inactivating, or transient, component of the Nav current (INaT) present in many types of central and peripheral neurons, Purkinje neurons, also expresses persistent (INaP) and resurgent (INaR) Nav currents. Considerable progress has been m...
Source: Cellular and Molecular Life Sciences : CMLS - July 7, 2018 Category: Cytology Authors: Ransdell JL, Nerbonne JM Tags: Cell Mol Life Sci Source Type: research

Dsg2 via Src-mediated transactivation shapes EGFR signaling towards cell adhesion.
aschke J Abstract Rapidly renewing epithelial tissues such as the intestinal epithelium require precise tuning of intercellular adhesion and proliferation to preserve barrier integrity. Here, we provide evidence that desmoglein 2 (Dsg2), an adhesion molecule of desmosomes, controls cell adhesion and proliferation via epidermal growth factor receptor (EGFR) signaling. Dsg2 is required for EGFR localization at intercellular junctions as well as for Src-mediated EGFR activation. Src binds to EGFR and is required for localization of EGFR and Dsg2 to cell-cell contacts. EGFR is critical for cell adhesion and barrier re...
Source: Cellular and Molecular Life Sciences : CMLS - July 6, 2018 Category: Cytology Authors: Ungewiß H, Rötzer V, Meir M, Fey C, Diefenbacher M, Schlegel N, Waschke J Tags: Cell Mol Life Sci Source Type: research

Crosstalk between metabolism and epigenetic modifications in autoimmune diseases: a comprehensive overview.
Abstract Little information is available regarding mechanistic links between epigenetic modifications and autoimmune diseases. It seems plausible to surmise that aberrant gene expression and energy metabolism would disrupt immune tolerance, which could ultimately result in autoimmune responses. Metaboloepigenetics is an emerging paradigm that defines the interrelationships between metabolism and epigenetics. Epigenetic modifications, such as the methylation/demethylation of DNA and histone proteins and histone acetylation/deacetylation can be dynamically produced and eliminated by a group of enzymes that consume s...
Source: Cellular and Molecular Life Sciences : CMLS - July 4, 2018 Category: Cytology Authors: Wang Z, Long H, Chang C, Zhao M, Lu Q Tags: Cell Mol Life Sci Source Type: research

Correction to: Cellular mechanisms responsible for cell-to-cell spreading of prions.
anc P Abstract In the original publication, part of acknowledgement text was missing. The complete acknowledgement section should read as follows. PMID: 29907937 [PubMed - in process] (Source: Cellular and Molecular Life Sciences : CMLS)
Source: Cellular and Molecular Life Sciences : CMLS - June 18, 2018 Category: Cytology Authors: Vilette D, Courte J, Peyrin JM, Coudert L, Schaeffer L, Andréoletti O, Leblanc P Tags: Cell Mol Life Sci Source Type: research

The role of survival motor neuron protein (SMN) in protein homeostasis.
Abstract Ever since loss of survival motor neuron (SMN) protein was identified as the direct cause of the childhood inherited neurodegenerative disorder spinal muscular atrophy, significant efforts have been made to reveal the molecular functions of this ubiquitously expressed protein. Resulting research demonstrated that SMN plays important roles in multiple fundamental cellular homeostatic pathways, including a well-characterised role in the assembly of the spliceosome and biogenesis of ribonucleoproteins. More recent studies have shown that SMN is also involved in other housekeeping processes, including mRNA tr...
Source: Cellular and Molecular Life Sciences : CMLS - June 5, 2018 Category: Cytology Authors: Chaytow H, Huang YT, Gillingwater TH, Faller KME Tags: Cell Mol Life Sci Source Type: research

Regulating the human HECT E3 ligases.
Abstract Ubiquitination, the covalent attachment of ubiquitin to proteins, by E3 ligases of the HECT (homologous to E6AP C terminus) family is critical in controlling diverse physiological pathways. Stringent control of HECT E3 ligase activity and substrate specificity is essential for cellular health, whereas deregulation of HECT E3s plays a prominent role in disease. The cell employs a wide variety of regulatory mechanisms to control HECT E3 activity and substrate specificity. Here, we summarize the current understanding of these regulatory mechanisms that control HECT E3 function. Substrate specificity is gener...
Source: Cellular and Molecular Life Sciences : CMLS - June 1, 2018 Category: Cytology Authors: Sluimer J, Distel B Tags: Cell Mol Life Sci Source Type: research

The adhesion receptor GPR56 is activated by extracellular matrix collagen III to improve β-cell function.
CONCLUSION: We have demonstrated that collagen III improves islet function by increasing insulin secretion and protecting against apoptosis. Our data suggest that collagen III may be effective in optimising islet function to improve islet transplantation outcomes, and GPR56 may be a target for the treatment of type 2 diabetes. PMID: 29855662 [PubMed - as supplied by publisher] (Source: Cellular and Molecular Life Sciences : CMLS)
Source: Cellular and Molecular Life Sciences : CMLS - May 31, 2018 Category: Cytology Authors: Olaniru OE, Pingitore A, Giera S, Piao X, Castañera González R, Jones PM, Persaud SJ Tags: Cell Mol Life Sci Source Type: research

Immune stimuli shape the small non-coding transcriptome of extracellular vesicles released by dendritic cells.
Abstract The release and uptake of nano-sized extracellular vesicles (EV) is a highly conserved means of intercellular communication. The molecular composition of EV, and thereby their signaling function to target cells, is regulated by cellular activation and differentiation stimuli. EV are regarded as snapshots of cells and are, therefore, in the limelight as biomarkers for disease. Although research on EV-associated RNA has predominantly focused on microRNAs, the transcriptome of EV consists of multiple classes of small non-coding RNAs with potential gene-regulatory functions. It is not known whether environmen...
Source: Cellular and Molecular Life Sciences : CMLS - May 28, 2018 Category: Cytology Authors: Driedonks TAP, van der Grein SG, Ariyurek Y, Buermans HPJ, Jekel H, Chow FWN, Wauben MHM, Buck AH, 't Hoen PAC, Nolte-'t Hoen ENM Tags: Cell Mol Life Sci Source Type: research

Maternal eating behavior is a major synchronizer of fetal and postnatal peripheral clocks in mice.
rut J Abstract Most living organisms show circadian rhythms in physiology and behavior. These oscillations are generated by endogenous circadian clocks, present in virtually all cells where they control key biological processes. To study peripheral clocks in vivo, we developed an original model, the Rev-Luc mouse to follow noninvasively and longitudinally Rev-Luc oscillations in peripheral clocks using in vivo bioluminescence imaging. We found in vitro and in vivo a robust diurnal rhythm of Rev-Luc, mainly in liver, intestine, kidney and adipose tissues. We further confirmed in vivo that Rev-Luc peripheral tissues...
Source: Cellular and Molecular Life Sciences : CMLS - May 26, 2018 Category: Cytology Authors: Canaple L, Gréchez-Cassiau A, Delaunay F, Dkhissi-Benyahya O, Samarut J Tags: Cell Mol Life Sci Source Type: research

Role of peroxisome proliferator-activated receptors in non-alcoholic fatty liver disease inflammation.
Abstract Overweight and obesity have been identified as the most important risk factors for many diseases, including cardiovascular disease, type 2 diabetes and lipid disorders, such as non-alcoholic fatty liver disease (NAFLD). The metabolic changes associated with obesity are grouped to define metabolic syndrome, which is one of the main causes of morbidity and mortality in industrialized countries. NAFLD is considered to be the hepatic manifestation of metabolic syndrome and is one of the most prevalent liver diseases worldwide. Inflammation plays an important role in the development of numerous liver diseases,...
Source: Cellular and Molecular Life Sciences : CMLS - May 22, 2018 Category: Cytology Authors: Silva AKS, Peixoto CA Tags: Cell Mol Life Sci Source Type: research

MAP kinase signalling: interplays between plant PAMP- and effector-triggered immunity.
Abstract In plants, mitogen-activated protein kinase (MAPK) cascades are involved in regulating many biological processes including immunity. They relay signals from membrane-residing immune receptors to downstream components for defense activation. Arabidopsis MPK3/6 and MPK4 are activated in two parallel MAPK cascades during PAMP-triggered immunity. MPK3/6 have been implicated in the activation of various immune responses and their inactivation leads to compromised defense against pathogens. On the other hand, the MEKK1-MKK1/2-MPK4 cascade plays critical roles in basal resistance. Disruption of this MAPK cascade...
Source: Cellular and Molecular Life Sciences : CMLS - May 22, 2018 Category: Cytology Authors: Thulasi Devendrakumar K, Li X, Zhang Y Tags: Cell Mol Life Sci Source Type: research

The potential importance of myeloid-derived suppressor cells (MDSCs) in the pathogenesis of Alzheimer's disease.
Abstract The exact cause of Alzheimer's disease (AD) is still unknown, but the deposition of amyloid-β (Aβ) plaques and chronic inflammation indicates that immune disturbances are involved in AD pathogenesis. Recent genetic studies have revealed that many candidate genes are expressed in both microglia and myeloid cells which infiltrate into the AD brains. Invading myeloid cells controls the functions of resident microglia in pathological conditions, such as AD pathology. AD is a neurologic disease with inflammatory component where the immune system is not able to eliminate the perpetrator, while, concur...
Source: Cellular and Molecular Life Sciences : CMLS - May 19, 2018 Category: Cytology Authors: Salminen A, Kaarniranta K, Kauppinen A Tags: Cell Mol Life Sci Source Type: research

Combining theoretical and experimental data to decipher CFTR 3D structures and functions.
aut I Abstract Cryo-electron microscopy (cryo-EM) has recently provided invaluable experimental data about the full-length cystic fibrosis transmembrane conductance regulator (CFTR) 3D structure. However, this experimental information deals with inactive states of the channel, either in an apo, quiescent conformation, in which nucleotide-binding domains (NBDs) are widely separated or in an ATP-bound, yet closed conformation. Here, we show that 3D structure models of the open and closed forms of the channel, now further supported by metadynamics simulations and by comparison with the cryo-EM data, could be used to ...
Source: Cellular and Molecular Life Sciences : CMLS - May 19, 2018 Category: Cytology Authors: Hoffmann B, Elbahnsi A, Lehn P, Décout JL, Pietrucci F, Mornon JP, Callebaut I Tags: Cell Mol Life Sci Source Type: research

GLIS1-3 transcription factors: critical roles in the regulation of multiple physiological processes and diseases.
Abstract Krüppel-like zinc finger proteins form one of the largest families of transcription factors. They function as key regulators of embryonic development and a wide range of other physiological processes, and are implicated in a variety of pathologies. GLI-similar 1-3 (GLIS1-3) constitute a subfamily of Krüppel-like zinc finger proteins that act either as activators or repressors of gene transcription. GLIS3 plays a critical role in the regulation of multiple biological processes and is a key regulator of pancreatic β cell generation and maturation, insulin gene expression, thyroid hormone bios...
Source: Cellular and Molecular Life Sciences : CMLS - May 19, 2018 Category: Cytology Authors: Jetten AM Tags: Cell Mol Life Sci Source Type: research

Mitochondrial quality control in AMD: does mitophagy play a pivotal role?
Abstract Age-related macular degeneration (AMD) is the predominant cause of visual loss in old people in the developed world, whose incidence is increasing. This disease is caused by the decrease in macular function, due to the degeneration of retinal pigment epithelium (RPE) cells. The aged retina is characterised by increased levels of reactive oxygen species (ROS), impaired autophagy, and DNA damage that are linked to AMD pathogenesis. Mitophagy, a mitochondria-specific type of autophagy, is an essential part of mitochondrial quality control, the collective mechanism responsible for this organelle's homeostasis...
Source: Cellular and Molecular Life Sciences : CMLS - May 18, 2018 Category: Cytology Authors: Hyttinen JMT, Viiri J, Kaarniranta K, Błasiak J Tags: Cell Mol Life Sci Source Type: research

Roles of heat shock factor 1 beyond the heat shock response.
Abstract Various stress factors leading to protein damage induce the activation of an evolutionarily conserved cell protective mechanism, the heat shock response (HSR), to maintain protein homeostasis in virtually all eukaryotic cells. Heat shock factor 1 (HSF1) plays a central role in the HSR. HSF1 was initially known as a transcription factor that upregulates genes encoding heat shock proteins (HSPs), also called molecular chaperones, which assist in refolding or degrading injured intracellular proteins. However, recent accumulating evidence indicates multiple additional functions for HSF1 beyond the activation ...
Source: Cellular and Molecular Life Sciences : CMLS - May 17, 2018 Category: Cytology Authors: Barna J, Csermely P, Vellai T Tags: Cell Mol Life Sci Source Type: research

Involvement of extrasynaptic glutamate in physiological and pathophysiological changes of neuronal excitability.
e;l B Abstract Glutamate is the most abundant neurotransmitter of the central nervous system, as the majority of neurons use glutamate as neurotransmitter. It is also well known that this neurotransmitter is not restricted to synaptic clefts, but found in the extrasynaptic regions as ambient glutamate. Extrasynaptic glutamate originates from spillover of synaptic release, as well as from astrocytes and microglia. Its concentration is magnitudes lower than in the synaptic cleft, but receptors responding to it have higher affinity for it. Extrasynaptic glutamate receptors can be found in neuronal somatodendritic loc...
Source: Cellular and Molecular Life Sciences : CMLS - May 15, 2018 Category: Cytology Authors: Pál B Tags: Cell Mol Life Sci Source Type: research

Cellular mechanisms responsible for cell-to-cell spreading of prions.
anc P Abstract Prions are infectious agents that cause fatal neurodegenerative diseases. Current evidence indicates that they are essentially composed of an abnormally folded protein (PrPSc). These abnormal aggregated PrPSc species multiply in infected cells by recruiting and converting the host PrPC protein into new PrPSc. How prions move from cell to cell and progressively spread across the infected tissue is of crucial importance and may provide experimental opportunity to delay the progression of the disease. In infected cells, different mechanisms have been identified, including release of infectious extracel...
Source: Cellular and Molecular Life Sciences : CMLS - May 14, 2018 Category: Cytology Authors: Vilette D, Courte J, Peyrin JM, Coudert L, Schaeffer L, Andréoletti O, Leblanc P Tags: Cell Mol Life Sci Source Type: research

Imaging of oxygen and hypoxia in cell and tissue samples.
Abstract Molecular oxygen (O2) is a key player in cell mitochondrial function, redox balance and oxidative stress, normal tissue function and many common disease states. Various chemical, physical and biological methods have been proposed for measurement, real-time monitoring and imaging of O2 concentration, state of decreased O2 (hypoxia) and related parameters in cells and tissue. Here, we review the established and emerging optical microscopy techniques allowing to visualize O2 levels in cells and tissue samples, mostly under in vitro and ex vivo, but also under in vivo settings. Particular examples include flu...
Source: Cellular and Molecular Life Sciences : CMLS - May 14, 2018 Category: Cytology Authors: Papkovsky DB, Dmitriev RI Tags: Cell Mol Life Sci Source Type: research

The capacity of oocytes for DNA repair.
Abstract Female fertility and offspring health are critically dependent on the maintenance of an adequate supply of high-quality oocytes. Like somatic cells, oocytes are subject to a variety of different types of DNA damage arising from endogenous cellular processes and exposure to exogenous genotoxic stressors. While the repair of intentionally induced DNA double strand breaks in gametes during meiotic recombination is well characterised, less is known about the ability of oocytes to repair pathological DNA damage and the relative contribution of DNA repair to oocyte quality is not well defined. This review will ...
Source: Cellular and Molecular Life Sciences : CMLS - May 10, 2018 Category: Cytology Authors: Stringer JM, Winship A, Liew SH, Hutt K Tags: Cell Mol Life Sci Source Type: research

Control of excessive neural circuit excitability and prevention of epileptic seizures by endocannabinoid signaling.
Abstract Progress in research on endocannabinoid signaling has greatly advanced our understanding of how it controls neural circuit excitability in health and disease. In general, endocannabinoid signaling at excitatory synapses suppresses seizures by inhibiting glutamate release. In contrast, endocannabinoid signaling promotes seizures by inhibiting GABA release at inhibitory synapses. The physiological distribution of endocannabinoid signaling molecules becomes disrupted with the development of epileptic focus in patients with mesial temporal lobe epilepsy and in animal models of experimentally induced epilepsy....
Source: Cellular and Molecular Life Sciences : CMLS - May 8, 2018 Category: Cytology Authors: Sugaya Y, Kano M Tags: Cell Mol Life Sci Source Type: research

Engineering microbes for targeted strikes against human pathogens.
Abstract Lack of pathogen specificity in antimicrobial therapy causes non-discriminant microbial cell killing that disrupts the microflora present. As a result, potentially helpful microbial cells are killed along with the pathogen, altering the biodiversity and dynamic interactions within the population. Moreover, the unwarranted exposure of antibiotics to microbes increases the likelihood of developing resistance and perpetuates the emergence of multidrug resistance. Synthetic biology offers an alternative solution where specificity can be conferred to reduce the non-specific, non-targeted activity of currently ...
Source: Cellular and Molecular Life Sciences : CMLS - May 7, 2018 Category: Cytology Authors: Hwang IY, Lee HL, Huang JG, Lim YY, Yew WS, Lee YS, Chang MW Tags: Cell Mol Life Sci Source Type: research

Seed coat thickness in the evolution of angiosperms.
Abstract The seed habit represents a remarkable evolutionary advance in plant sexual reproduction. Since the Paleozoic, seeds carry a seed coat that protects, nourishes and facilitates the dispersal of the fertilization product(s). The seed coat architecture evolved to adapt to different environments and reproductive strategies in part by modifying its thickness. Here, we review the great natural diversity observed in seed coat thickness among angiosperms and its molecular regulation in Arabidopsis. PMID: 29730767 [PubMed - as supplied by publisher] (Source: Cellular and Molecular Life Sciences : CMLS)
Source: Cellular and Molecular Life Sciences : CMLS - May 5, 2018 Category: Cytology Authors: Coen O, Magnani E Tags: Cell Mol Life Sci Source Type: research

Proliferation of hippocampal progenitors relies on p27-dependent regulation of Cdk6 kinase activity.
Abstract Neural stem cells give rise to granule dentate neurons throughout life in the hippocampus. Upon activation, these stem cells generate fast proliferating progenitors that complete several rounds of divisions before differentiating into neurons. Although the mechanisms regulating the activation of stem cells have been intensively studied, little attention has been given so far to the intrinsic machinery allowing the expansion of the progenitor pool. The cell cycle protein Cdk6 positively regulates the proliferation of hippocampal progenitors, but the mechanism involved remains elusive. Whereas Cdk6 function...
Source: Cellular and Molecular Life Sciences : CMLS - May 4, 2018 Category: Cytology Authors: Caron N, Genin EC, Marlier Q, Verteneuil S, Beukelaers P, Morel L, Hu MG, Hinds PW, Nguyen L, Vandenbosch R, Malgrange B Tags: Cell Mol Life Sci Source Type: research

Why the impact of mechanical stimuli on stem cells remains a challenge.
Abstract Mechanical stimulation affects growth and differentiation of stem cells. This may be used to guide lineage-specific cell fate decisions and therefore opens fascinating opportunities for stem cell biology and regenerative medicine. Several studies demonstrated functional and molecular effects of mechanical stimulation but on first sight these results often appear to be inconsistent. Comparison of such studies is hampered by a multitude of relevant parameters that act in concert. There are notorious differences between species, cell types, and culture conditions. Furthermore, the utilized culture substrates...
Source: Cellular and Molecular Life Sciences : CMLS - May 4, 2018 Category: Cytology Authors: Goetzke R, Sechi A, De Laporte L, Neuss S, Wagner W Tags: Cell Mol Life Sci Source Type: research

Including the mitochondrial metabolism of L-lactate in cancer metabolic reprogramming.
Abstract Glucose avidity, high glycolysis and L-lactate production, regardless of oxygen availability, are the main traits of cancer metabolic reprogramming. The idea that mitochondria are dysfunctional in cancer, thus causing a glycolysis increase for ATP production and L-lactate accumulation as a dead-end product of glucose catabolism, has oriented cancer research for many years. However, it was shown that mitochondrial metabolism is essential for cancer cell proliferation and tumorigenesis and that L-lactate is a fundamental energy substrate with tumor growth-promoting and signaling capabilities. Nevertheless, ...
Source: Cellular and Molecular Life Sciences : CMLS - May 4, 2018 Category: Cytology Authors: de Bari L, Atlante A Tags: Cell Mol Life Sci Source Type: research

The impact of phosphatases on proliferative and survival signaling in cancer.
Abstract The dynamic and stringent coordination of kinase and phosphatase activity controls a myriad of physiologic processes. Aberrations that disrupt the balance of this interplay represent the basis of numerous diseases. For a variety of reasons, early work in this area portrayed kinases as the dominant actors in these signaling events with phosphatases playing a secondary role. In oncology, these efforts led to breakthroughs that have dramatically altered the course of certain diseases and directed vast resources toward the development of additional kinase-targeted therapies. Yet, more recent scientific effort...
Source: Cellular and Molecular Life Sciences : CMLS - May 3, 2018 Category: Cytology Authors: Narla G, Sangodkar J, Ryder CB Tags: Cell Mol Life Sci Source Type: research

Fibroblast growth factor receptor 1 signaling transcriptionally regulates the axon guidance cue slit1.
We examined here the transcriptional regulation of the guidance gene slit1 both in vitro and in vivo by specific fibroblast growth factor receptors (Fgfrs). We identified an Fgf-responsive 2.3 kb slit1 promoter sequence that recapitulates spatiotemporal endogenous expression in the neural tube and eye of Xenopus embryos. We found that signaling through Fgfr1 is the main regulator of slit1 expression both in vitro in A6 kidney epithelial cells, and in the Xenopus forebrain, even when other Fgfr subtypes are present in cells. These data argue that a specific signaling pathway downstream of Fgfr1 controls in a cell-auton...
Source: Cellular and Molecular Life Sciences : CMLS - April 28, 2018 Category: Cytology Authors: Yang JJ, Bertolesi GE, Hehr CL, Johnston J, McFarlane S Tags: Cell Mol Life Sci Source Type: research

Phosphatidylinositol-3,5-bisphosphate lipid-binding-induced activation of the human two-pore channel 2.
h P Abstract Mammalian two-pore channels (TPCs) are activated by the low-abundance membrane lipid phosphatidyl-(3,5)-bisphosphate (PI(3,5)P2) present in the endo-lysosomal system. Malfunction of human TPC1 or TPC2 (hTPC) results in severe organellar storage diseases and membrane trafficking defects. Here, we compared the lipid-binding characteristics of hTPC2 and of the PI(3,5)P2-insensitive TPC1 from the model plant Arabidopsis thaliana. Combination of simulations with functional analysis of channel mutants revealed the presence of an hTPC2-specific lipid-binding pocket mutually formed by two channel regions expo...
Source: Cellular and Molecular Life Sciences : CMLS - April 28, 2018 Category: Cytology Authors: Kirsch SA, Kugemann A, Carpaneto A, Böckmann RA, Dietrich P Tags: Cell Mol Life Sci Source Type: research

Impact of late-onset Alzheimer's genetic risk factors on beta-amyloid endocytic production.
nha T Abstract The increased production of the 42 aminoacids long beta-amyloid (Aβ42) peptide has been established as a causal mechanism of the familial early onset Alzheimer's disease (AD). In contrast, the causal mechanisms of the late-onset AD (LOAD), that affects most AD patients, remain to be established. Indeed, Aβ42 accumulation has been detected more than 30 years before diagnosis. Thus, the mechanisms that control Aβ accumulation in LOAD likely go awry long before pathogenesis becomes detectable. Early on, APOE4 was identified as the biggest genetic risk factor for LOAD. However, since...
Source: Cellular and Molecular Life Sciences : CMLS - April 27, 2018 Category: Cytology Authors: Guimas Almeida C, Sadat Mirfakhar F, Perdigão C, Burrinha T Tags: Cell Mol Life Sci Source Type: research

Functional characterisation of naturally occurring mutations in human melanopsin.
Abstract Melanopsin is a blue light-sensitive opsin photopigment involved in a range of non-image forming behaviours, including circadian photoentrainment and the pupil light response. Many naturally occurring genetic variants exist within the human melanopsin gene (OPN4), yet it remains unclear how these variants affect melanopsin protein function and downstream physiological responses to light. Here, we have used bioinformatic analysis and in vitro expression systems to determine the functional phenotypes of missense human OPN4 variants. From 1242 human OPN4 variants collated in the NCBI Short Genetic Variation ...
Source: Cellular and Molecular Life Sciences : CMLS - April 26, 2018 Category: Cytology Authors: Rodgers J, Peirson SN, Hughes S, Hankins MW Tags: Cell Mol Life Sci Source Type: research

PAR3-PAR6-atypical PKC polarity complex proteins in neuronal polarization.
Abstract Polarity is a fundamental feature of cells. Protein complexes, including the PAR3-PAR6-aPKC complex, have conserved roles in establishing polarity across a number of eukaryotic cell types. In neurons, polarity is evident as distinct axonal versus dendritic domains. The PAR3, PAR6, and aPKC proteins also play important roles in neuronal polarization. During this process, either aPKC kinase activity, the assembly of the PAR3-PAR6-aPKC complex or the localization of these proteins is regulated downstream of a number of signaling pathways. In turn, the PAR3, PAR6, and aPKC proteins control various effector mo...
Source: Cellular and Molecular Life Sciences : CMLS - April 25, 2018 Category: Cytology Authors: Hapak SM, Rothlin CV, Ghosh S Tags: Cell Mol Life Sci Source Type: research