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

Enhancer reprogramming in tumor progression: a new route towards cancer cell plasticity.
Abstract Cancer heterogeneity arises during tumor progression as a consequence of genetic insults, environmental cues, and reversible changes in the epigenetic state, favoring tumor cell plasticity. The role of enhancer reprogramming is emerging as a relevant field in cancer biology as it supports adaptation of cancer cells to those environmental changes encountered during tumor progression and metastasis seeding. In this review, we describe the cancer-related alterations that drive oncogenic enhancer activity, leading to dysregulated transcriptional programs. We discuss the molecular mechanisms of both cis- and t...
Source: Cellular and Molecular Life Sciences : CMLS - April 24, 2018 Category: Cytology Authors: Fagnocchi L, Poli V, Zippo A Tags: Cell Mol Life Sci Source Type: research

Author Correction: Melatonin and mitochondrial function during ischemia/reperfusion injury.
Abstract In the original publication, affiliations were incorrectly published for the authors. PMID: 29691591 [PubMed - as supplied by publisher] (Source: Cellular and Molecular Life Sciences : CMLS)
Source: Cellular and Molecular Life Sciences : CMLS - April 24, 2018 Category: Cytology Authors: Ma Z, Xin Z, Di W, Yan X, Li X, Reiter RJ, Yang Y Tags: Cell Mol Life Sci Source Type: research

Ciliary proteins Fap43 and Fap44 interact with each other and are essential for proper cilia and flagella beating.
Abstract Cilia beating is powered by the inner and outer dynein arms (IDAs and ODAs). These multi-subunit macrocomplexes are arranged in two rows on each outer doublet along the entire cilium length, except its distal end. To generate cilia beating, the activity of ODAs and IDAs must be strictly regulated locally by interactions with the dynein arm-associated structures within each ciliary unit and coordinated globally in time and space between doublets and along the axoneme. Here, we provide evidence of a novel ciliary complex composed of two conserved WD-repeat proteins, Fap43p and Fap44p. This complex is adjace...
Source: Cellular and Molecular Life Sciences : CMLS - April 23, 2018 Category: Cytology Authors: Urbanska P, Joachimiak E, Bazan R, Fu G, Poprzeczko M, Fabczak H, Nicastro D, Wloga D Tags: Cell Mol Life Sci Source Type: research

Micromanaging freeze tolerance: the biogenesis and regulation of neuroprotective microRNAs in frozen brains.
Abstract When temperatures plummet below 0 °C, wood frogs (Rana sylvatica) can endure the freezing of up to ~ 65% of their body water in extracellular ice masses, displaying no measurable brain activity, no breathing, no movement, and a flat-lined heart. To aid survival, frogs retreat into a state of suspended animation characterized by global suppression of metabolic functions and reprioritization of energy usage to essential survival processes that is elicited, in part, by the regulatory controls of microRNAs. The present study is the first to investigate miRNA biogenesis and regulation in...
Source: Cellular and Molecular Life Sciences : CMLS - April 21, 2018 Category: Cytology Authors: Hadj-Moussa H, Storey KB Tags: Cell Mol Life Sci Source Type: research

Depletion of angiotensin-converting enzyme 2 reduces brain serotonin and impairs the running-induced neurogenic response.
Abstract Physical exercise induces cell proliferation in the adult hippocampus in rodents. Serotonin (5-HT) and angiotensin (Ang) II are important mediators of the pro-mitotic effect of physical activity. Here, we examine precursor cells in the adult brain of mice lacking angiotensin-converting enzyme (ACE) 2, and explore the effect of an acute running stimulus on neurogenesis. ACE2 metabolizes Ang II to Ang-(1-7) and is essential for the intestinal uptake of tryptophan (Trp), the 5-HT precursor. In ACE2-deficient mice, we observed a decrease in brain 5-HT levels and no increase in the number of BrdU-positive cell...
Source: Cellular and Molecular Life Sciences : CMLS - April 20, 2018 Category: Cytology Authors: Klempin F, Mosienko V, Matthes S, Villela DC, Todiras M, Penninger JM, Bader M, Santos RAS, Alenina N Tags: Cell Mol Life Sci Source Type: research

Implication of the VRK1 chromatin kinase in the signaling responses to DNA damage: a therapeutic target?
Abstract DNA damage causes a local distortion of chromatin that triggers the sequential processes that participate in specific DNA repair mechanisms. This initiation of the repair response requires the involvement of a protein whose activity can be regulated by histones. Kinases are candidates to regulate and coordinate the connection between a locally altered chromatin and the response initiating signals that lead to identification of the type of lesion and the sequential steps required in specific DNA damage responses (DDR). This initiating kinase must be located in chromatin, and be activated independently of t...
Source: Cellular and Molecular Life Sciences : CMLS - April 20, 2018 Category: Cytology Authors: Campillo-Marcos I, Lazo PA Tags: Cell Mol Life Sci Source Type: research

Neuronal autophagy and axon degeneration.
Abstract Axon degeneration is a pathophysiological process of axonal dying and breakdown, which is characterized by several morphological features including the accumulation of axoplasmic organelles, disassembly of microtubules, and fragmentation of the axonal cytoskeleton. Autophagy, a highly conserved lysosomal-degradation machinery responsible for the control of cellular protein quality, is widely believed to be essential for the maintenance of axonal homeostasis in neurons. In recent years, more and more evidence suggests that dysfunctional autophagy is associated with axonal degeneration in many neurodegenera...
Source: Cellular and Molecular Life Sciences : CMLS - April 19, 2018 Category: Cytology Authors: Wang Y, Song M, Song F Tags: Cell Mol Life Sci Source Type: research

Approaches to identify and characterize microProteins and their potential uses in biotechnology.
Abstract MicroProteins are small proteins that contain a single protein domain and are related to larger, often multi-domain proteins. At the molecular level, microProteins act by interfering with the formation of higher order protein complexes. In the past years, several microProteins have been identified in plants and animals that strongly influence biological processes. Due to their ability to act as dominant regulators in a targeted manner, microProteins have a high potential for biotechnological use. In this review, we present different ways in which microProteins are generated and we elaborate on techniques ...
Source: Cellular and Molecular Life Sciences : CMLS - April 18, 2018 Category: Cytology Authors: Bhati KK, Blaakmeer A, Paredes EB, Dolde U, Eguen T, Hong SY, Rodrigues V, Straub D, Sun B, Wenkel S Tags: Cell Mol Life Sci Source Type: research

Mechanisms involved in normal and pathological osteoclastogenesis.
Abstract Osteoclasts are bone-resorbing cells that play an essential role in bone remodeling. Defects in osteoclasts result in unbalanced bone remodeling and are linked to many bone diseases including osteoporosis, rheumatoid arthritis, primary bone cancer, and skeletal metastases. Receptor activator of NF-kappaB ligand (RANKL) is a classical inducer of osteoclast formation. In the presence of macrophage-colony-stimulating factor, RANKL and co-stimulatory signals synergistically regulate osteoclastogenesis. However, recent discoveries of alternative pathways for RANKL-independent osteoclastogenesis have led to a r...
Source: Cellular and Molecular Life Sciences : CMLS - April 18, 2018 Category: Cytology Authors: Park-Min KH Tags: Cell Mol Life Sci Source Type: research

Author Correction: Intrinsic links among sex, emotion, and reproduction.
Abstract Species survival is dependent on successful reproduction. This begins with a desire to mate, followed by selection of a partner, copulation and in monogamous mammals including humans. PMID: 29666877 [PubMed - as supplied by publisher] (Source: Cellular and Molecular Life Sciences : CMLS)
Source: Cellular and Molecular Life Sciences : CMLS - April 17, 2018 Category: Cytology Authors: Yang L, Comninos AN, Dhillo WS Tags: Cell Mol Life Sci Source Type: research

Engineering CRISPR/Cpf1 with tRNA promotes genome editing capability in mammalian systems.
In this study, we designed and optimized a guide RNA (gRNA) transcription system by inserting a transfer RNA precursor (pre-tRNA) sequence downstream of the gRNA for Cpf1, protecting gRNA from immediate digestion by 3'-to-5' exonucleases. Using this new gRNAtRNA system, genome editing, including indels, large fragment deletion and precise point mutation, was induced in mammalian systems, showing significantly higher efficiency than the original Cpf1-gRNA system. With this system, gene-modified rabbits and pigs were generated by embryo injection or somatic cell nuclear transfer (SCNT) with an efficiency comparable to that o...
Source: Cellular and Molecular Life Sciences : CMLS - April 10, 2018 Category: Cytology Authors: Wu H, Liu Q, Shi H, Xie J, Zhang Q, Ouyang Z, Li N, Yang Y, Liu Z, Zhao Y, Lai C, Ruan D, Peng J, Ge W, Chen F, Fan N, Jin Q, Liang Y, Lan T, Yang X, Wang X, Lei Z, Doevendans PA, Sluijter JPG, Wang K, Li X, Lai L Tags: Cell Mol Life Sci Source Type: research

The functional analysis of SlNCED1 in tomato pollen development.
Abstract Abscisic acid (ABA) regulates plant growth and development, but the role of ABA in the development of reproductive organs in tomato has rarely been addressed. In the present study, the role of ABA in the regulation of male and female gametogenesis as well as pollen development and germination is tested in tomato. qRT-PCR and in situ hybridization analysis of 9-cis-epoxycarotenoid dioxygenase (SlNCED1), a key enzyme in the ABA biosynthetic pathway, showed high expression of SlNCED1 primarily in the meristem during gametogenesis and mainly in ovule, stigma, anther/pollen and vascular tissues during floral o...
Source: Cellular and Molecular Life Sciences : CMLS - April 9, 2018 Category: Cytology Authors: Dai S, Kai W, Liang B, Wang J, Jiang L, Du Y, Sun Y, Leng P Tags: Cell Mol Life Sci Source Type: research

A latent ability to persist: differentiation in Toxoplasma gondii.
Abstract A critical factor in the transmission and pathogenesis of Toxoplasma gondii is the ability to convert from an acute disease-causing, proliferative stage (tachyzoite), to a chronic, dormant stage (bradyzoite). The conversion of the tachyzoite-containing parasitophorous vacuole membrane into the less permeable bradyzoite cyst wall allows the parasite to persist for years within the host to maximize transmissibility to both primary (felids) and secondary (virtually all other warm-blooded vertebrates) hosts. This review presents our current understanding of the latent stage, including the factors that are imp...
Source: Cellular and Molecular Life Sciences : CMLS - March 30, 2018 Category: Cytology Authors: Jeffers V, Tampaki Z, Kim K, Sullivan WJ Tags: Cell Mol Life Sci Source Type: research

Regulation of the Hippo pathway in cancer biology.
Abstract The Hippo tumor suppressor pathway, which is well conserved from Drosophila to humans, has emerged as the master regulator of organ size, as well as major cellular properties, such as cell proliferation, survival, stemness, and tissue homeostasis. The biological significance and deregulation of the Hippo pathway in tumorigenesis have received a surge of interest in the past decade. In the current review, we present the major discoveries that made substantial contributions to our understanding of the Hippo pathway and discuss how Hippo pathway components contribute to cellular signaling, physiology, and th...
Source: Cellular and Molecular Life Sciences : CMLS - March 30, 2018 Category: Cytology Authors: Moon S, Yeon Park S, Woo Park H Tags: Cell Mol Life Sci Source Type: research

Follistatin-like 1 in development and human diseases.
Abstract Follistatin-like 1 (FSTL1) is a secreted glycoprotein displaying expression changes during development and disease, among which cardiovascular disease, cancer, and arthritis. The cardioprotective role of FSTL1 has been intensively studied over the last years, though its mechanism of action remains elusive. FSTL1 is involved in multiple signaling pathways and biological processes, including vascularization and regulation of the immune response, a feature that complicates its study. Binding to the DIP2A, TLR4 and BMP receptors have been shown, but other molecular partners probably exist. During cancer progr...
Source: Cellular and Molecular Life Sciences : CMLS - March 29, 2018 Category: Cytology Authors: Mattiotti A, Prakash S, Barnett P, van den Hoff MJB Tags: Cell Mol Life Sci Source Type: research

Redox-dependent thiol modifications: implications for the release of extracellular vesicles.
Abstract Extracellular vesicles (EVs), including microvesicles and exosomes, are emerging as important regulators of homeostasis and pathophysiology. During pro-inflammatory and pro-oxidant conditions, EV release is induced. As EVs released under such conditions often exert pro-inflammatory and procoagulant effects, they may actively promote the pathogenesis of chronic diseases. There is evidence that thiol group-containing antioxidants can prevent EV induction by pro-inflammatory and oxidative stimuli, likely by protecting protein thiols of the EV-secreting cells from oxidation. As the redox state of protein thio...
Source: Cellular and Molecular Life Sciences : CMLS - March 28, 2018 Category: Cytology Authors: Benedikter BJ, Weseler AR, Wouters EFM, Savelkoul PHM, Rohde GGU, Stassen FRM Tags: Cell Mol Life Sci Source Type: research

The insulin-degrading enzyme is an allosteric modulator of the 20S proteasome and a potential competitor of the 19S.
Abstract The interaction of insulin-degrading enzyme (IDE) with the main intracellular proteasome assemblies (i.e, 30S, 26S and 20S) was analyzed by enzymatic activity, mass spectrometry and native gel electrophoresis. IDE was mainly detected in association with assemblies with at least one free 20S end and biochemical investigations suggest that IDE competes with the 19S in vitro. IDE directly binds the 20S and affects its proteolytic activities in a bimodal fashion, very similar in human and yeast 20S, inhibiting at (IDE) ≤ 30 nM and activating at (IDE) ≥ 30 nM. Only a...
Source: Cellular and Molecular Life Sciences : CMLS - March 28, 2018 Category: Cytology Authors: Sbardella D, Tundo GR, Coletta A, Marcoux J, Koufogeorgou EI, Ciaccio C, Santoro AM, Milardi D, Grasso G, Cozza P, Bousquet-Dubouch MP, Marini S, Coletta M Tags: Cell Mol Life Sci Source Type: research

Tetraspanin-enriched microdomains regulate digitation junctions.
Abstract Tetraspanins co-emerged with multi-cellular organisms during evolution are typically localized at the cell-cell interface, and form tetraspanin-enriched microdomains (TEMs) by associating with each other and other membrane molecules. Tetraspanins affect various biological functions, but how tetraspanins engage in multi-faceted functions at the cellular level is largely unknown. When cells interact, the membrane microextrusions at the cell-cell interfaces form dynamic, digit-like structures between cells, which we term digitation junctions (DJs). We found that (1) tetraspanins CD9, CD81, and CD82 and (2) T...
Source: Cellular and Molecular Life Sciences : CMLS - March 27, 2018 Category: Cytology Authors: Huang C, Fu C, Wren JD, Wang X, Zhang F, Zhang YH, Connel SA, Chen T, Zhang XA Tags: Cell Mol Life Sci Source Type: research