Concerns regarding Baksa B, Kovacs A, Bayasgalan T, Szentesi P, Koseghy A, Szucs P, Balazs P. Characterization of functional subgroups among genetically identified cholinergic neurons in the pedunculopontine nucleus. Cell Molec. Life Sci. 2019-04-02.
PMID: 31570964 [PubMed - as supplied by publisher] (Source: Cellular and Molecular Life Sciences : CMLS)
Source: Cellular and Molecular Life Sciences : CMLS - September 30, 2019 Category: Cytology Authors: Garcia-Rill E, Urbano FJ Tags: Cell Mol Life Sci Source Type: research

Zeta-crystallin: a moonlighting player in cancer.
Abstract Crystallins were firstly found as structural proteins of the eye lens. To this family belong proteins, such as ζ-crystallin, expressed ubiquitously, and endowed with enzyme activity. ζ-crystallin is a moonlighting protein endowed with two main different functions: (1) mRNA binding with stabilizing activity; (2) NADPH:quinone oxidoreductase. ζ-crystallin has been clearly demonstrated to stabilize mRNAs encoding proteins involved in renal glutamine catabolism during metabolic acidosis resulting in ammoniagenesis and bicarbonate ion production that concur to compensate such condition. &ze...
Source: Cellular and Molecular Life Sciences : CMLS - September 28, 2019 Category: Cytology Authors: Lulli M, Nencioni D, Papucci L, Schiavone N Tags: Cell Mol Life Sci Source Type: research

Molecular and cellular evolution of corticogenesis in amniotes.
ell V Abstract The cerebral cortex varies dramatically in size and complexity between amniotes due to differences in neuron number and composition. These differences emerge during embryonic development as a result of variations in neurogenesis, which are thought to recapitulate modifications occurred during evolution that culminated in the human neocortex. Here, we review work from the last few decades leading to our current understanding of the evolution of neurogenesis and size of the cerebral cortex. Focused on specific examples across vertebrate and amniote phylogeny, we discuss developmental mechanisms regula...
Source: Cellular and Molecular Life Sciences : CMLS - September 28, 2019 Category: Cytology Authors: Cárdenas A, Borrell V Tags: Cell Mol Life Sci Source Type: research

Molecular determinants of mesenchymal cell activation in fibroproliferative diseases.
Abstract Uncontrolled scarring, or fibrosis, can interfere with the normal function of virtually all tissues of the body, ultimately leading to organ failure and death. Fibrotic diseases represent a major cause of death in industrialized countries. Unfortunately, no curative treatments for these conditions are yet available, highlighting the critical need for a better fundamental understanding of molecular mechanisms that may be therapeutically tractable. The ultimate indispensable effector cells responsible for deposition of extracellular matrix proteins that comprise scars are mesenchymal cells, namely fibroblas...
Source: Cellular and Molecular Life Sciences : CMLS - September 28, 2019 Category: Cytology Authors: Penke LR, Peters-Golden M Tags: Cell Mol Life Sci Source Type: research

Multifunctional nanomedicines for targeting epidermal growth factor receptor in colorectal cancer.
Abstract Systemic administration of chemotherapeutics by nanocarriers (NCs) functionalized with targeting agents provides a localized accumulation of drugs in the target tissues and cells. Advanced nanoscaled medicaments can enter into the tumor microenvironment (TME) and overcome the uniquely dysregulated biological settings of TME, including highly pressurized tumor interstitial fluid in an acidic milieu. Such multimodal nanomedicines seem to be one of the most effective treatment modalities against solid tumors such as colorectal cancer (CRC). To progress and invade, cancer cells overexpress various oncogenes a...
Source: Cellular and Molecular Life Sciences : CMLS - September 28, 2019 Category: Cytology Authors: Akbarzadeh Khiavi M, Safary A, Barar J, Ajoolabady A, Somi MH, Omidi Y Tags: Cell Mol Life Sci Source Type: research

The Drosophila odorant-binding protein 28a is involved in the detection of the floral odour ß-ionone.
The Drosophila odorant-binding protein 28a is involved in the detection of the floral odour ß-ionone. Cell Mol Life Sci. 2019 Sep 28;: Authors: Gonzalez D, Rihani K, Neiers F, Poirier N, Fraichard S, Gotthard G, Chertemps T, Maïbèche M, Ferveur JF, Briand L Abstract Odorant-binding proteins (OBPs) are small soluble proteins that are thought to transport hydrophobic odorants across the aqueous sensillar lymph to olfactory receptors. A recent study revealed that OBP28a, one of the most abundant Drosophila OBPs, is not required for odorant transport, but acts in buffering rapid odour va...
Source: Cellular and Molecular Life Sciences : CMLS - September 28, 2019 Category: Cytology Authors: Gonzalez D, Rihani K, Neiers F, Poirier N, Fraichard S, Gotthard G, Chertemps T, Maïbèche M, Ferveur JF, Briand L Tags: Cell Mol Life Sci Source Type: research

Global phosphoproteomic analysis of Ebola virions reveals a novel role for VP35 phosphorylation-dependent regulation of genome transcription.
Abstract Ebola virus (EBOV) causes severe human disease with a high case fatality rate. The balance of evidence implies that the virus circulates in bats. The molecular basis for host-viral interactions, including the role for phosphorylation during infections, is largely undescribed. To address this, and to better understand the biology of EBOV, the phosphorylation of EBOV proteins was analyzed in virions purified from infected monkey Vero-E6 cells and bat EpoNi/22.1 cells using high-resolution mass spectrometry. All EBOV structural proteins were detected with high coverage, along with phosphopeptides. Phosphoryl...
Source: Cellular and Molecular Life Sciences : CMLS - September 28, 2019 Category: Cytology Authors: Ivanov A, Ramanathan P, Parry C, Ilinykh PA, Lin X, Petukhov M, Obukhov Y, Ammosova T, Amarasinghe GK, Bukreyev A, Nekhai S Tags: Cell Mol Life Sci Source Type: research

Insights into the non-mitotic functions of Aurora kinase A: more than just cell division.
Abstract AURKA is a serine/threonine kinase overexpressed in several cancers. Originally identified as a protein with multifaceted roles during mitosis, improvements in quantitative microscopy uncovered several non-mitotic roles as well. In physiological conditions, AURKA regulates cilia disassembly, neurite extension, cell motility, DNA replication and senescence programs. In cancer-like contexts, AURKA actively promotes DNA repair, it acts as a transcription factor, promotes cell migration and invasion, and it localises at mitochondria to regulate mitochondrial dynamics and ATP production. Here we review the non...
Source: Cellular and Molecular Life Sciences : CMLS - September 27, 2019 Category: Cytology Authors: Bertolin G, Tramier M Tags: Cell Mol Life Sci Source Type: research

Purpurin modulates Tau-derived VQIVYK fibrillization and ameliorates Alzheimer's disease-like symptoms in animal model.
Abstract Neurofibrillary tangles of the Tau protein and plaques of the amyloid β peptide are hallmarks of Alzheimer's disease (AD), which is characterized by the conversion of monomeric proteins/peptides into misfolded β-sheet rich fibrils. Halting the fibrillation process and disrupting the existing aggregates are key challenges for AD drug development. Previously, we performed in vitro high-throughput screening for the identification of potent inhibitors of Tau aggregation using a proxy model, a highly aggregation-prone hexapeptide fragment 306VQIVYK311 (termed PHF6) derived from Tau. Here we have char...
Source: Cellular and Molecular Life Sciences : CMLS - September 27, 2019 Category: Cytology Authors: Viswanathan GK, Shwartz D, Losev Y, Arad E, Shemesh C, Pichinuk E, Engel H, Raveh A, Jelinek R, Cooper I, Gosselet F, Gazit E, Segal D Tags: Cell Mol Life Sci Source Type: research

Fbxl17 is rearranged in breast cancer and loss of its activity leads to increased global O-GlcNAcylation.
Abstract In cancer, many genes are mutated by genome rearrangement, but our understanding of the functional consequences of this remains rudimentary. Here we report the F-box protein encoded by FBXL17 is disrupted in the region of the gene that encodes its substrate-binding leucine rich repeat (LRR) domain. Truncating Fbxl17 LRRs impaired its association with the other SCF holoenzyme subunits Skp1, Cul1 and Rbx1, and decreased ubiquitination activity. Loss of the LRRs also differentially affected Fbxl17 binding to its targets. Thus, genomic rearrangements in FBXL17 are likely to disrupt SCFFbxl17-regulated network...
Source: Cellular and Molecular Life Sciences : CMLS - September 27, 2019 Category: Cytology Authors: Mason B, Flach S, Teixeira FR, Manzano Garcia R, Rueda OM, Abraham JE, Caldas C, Edwards PAW, Laman H Tags: Cell Mol Life Sci Source Type: research

The vertebrate tail: a gene playground for evolution.
Abstract The tail of all vertebrates, regardless of size and anatomical detail, derive from a post-anal extension of the embryo known as the tail bud. Formation, growth and differentiation of this structure are closely associated with the activity of a group of cells that derive from the axial progenitors that build the spinal cord and the muscle-skeletal case of the trunk. Gdf11 activity switches the development of these progenitors from a trunk to a tail bud mode by changing the regulatory network that controls their growth and differentiation potential. Recent work in the mouse indicates that the tail bud regul...
Source: Cellular and Molecular Life Sciences : CMLS - September 26, 2019 Category: Cytology Authors: Mallo M Tags: Cell Mol Life Sci Source Type: research

Targeting Hsp70 facilitated protein quality control for treatment of polyglutamine diseases.
Abstract The polyglutamine (polyQ) diseases are a group of nine fatal, adult-onset neurodegenerative disorders characterized by the misfolding and aggregation of mutant proteins containing toxic expansions of CAG/polyQ tracts. The heat shock protein 90 and 70 (Hsp90/Hsp70) chaperone machinery is a key component of cellular protein quality control, playing a role in the regulation of folding, aggregation, and degradation of polyQ proteins. The ability of Hsp70 to facilitate disaggregation and degradation of misfolded proteins makes it an attractive therapeutic target in polyQ diseases. Genetic studies have demonstr...
Source: Cellular and Molecular Life Sciences : CMLS - September 24, 2019 Category: Cytology Authors: Davis AK, Pratt WB, Lieberman AP, Osawa Y Tags: Cell Mol Life Sci Source Type: research

Bacterial stress defense: the crucial role of ribosome speed.
Abstract In nature, bacteria are constantly adapting to various stressful conditions. Timely activation of stress response programs is crucial for bacteria to smoothly survive under stressful conditions. Stress response, demanding the de novo synthesis of many defense proteins, is generally activated at the transcriptional level by specific regulators. However, the effect of the global protein translational status on stress response has been largely overlooked. The translational capacity is limited by the number of translating ribosomes and the translational elongation rate. Recent work has shown that certain envi...
Source: Cellular and Molecular Life Sciences : CMLS - September 24, 2019 Category: Cytology Authors: Zhu M, Dai X Tags: Cell Mol Life Sci Source Type: research

Deciphering structure, function and mechanism of lysine acetyltransferase HBO1 in protein acetylation, transcription regulation, DNA replication and its oncogenic properties in cancer.
Abstract HBO1 complexes are major acetyltransferase responsible for histone H4 acetylation in vivo, which belongs to the MYST family. As the core catalytic subunit, HBO1 consists of an N-terminal domain and a C-terminal MYST domain that are in charge of acetyl-CoA binding and acetylation reaction. HBO1 complexes are multimeric and normally consist of two native subunits MEAF6, ING4 or ING5 and two kinds of cofactors as chromatin reader: Jade-1/2/3 and BRPF1/2/3. The choices of subunits to form the HBO1 complexes provide a regulatory switch to potentiate its activity between histone H4 and H3 tails. Thus, HBO1 comp...
Source: Cellular and Molecular Life Sciences : CMLS - September 18, 2019 Category: Cytology Authors: Lan R, Wang Q Tags: Cell Mol Life Sci Source Type: research

Evidence for miR-548c-5p regulation of FOXC2 transcription through a distal genomic target site in human podocytes.
Abstract Podocytes are highly differentiated epithelial cells outlining the glomerular vessels. FOXC2 is a transcription factor essential for inducing podocyte differentiation, development and maturation, and is considered to be the earliest podocyte marker. miRNA prediction analysis revealed a full-length target site for the primate-specific miR-548c-5p at a genomic region > 8 kb upstream of FOXC2. We hypothesised that the transcription rates of FOXC2 during podocyte differentiation might be tuned by miR-548c-5p through this target site. Experiments were performed with cultured human podocyt...
Source: Cellular and Molecular Life Sciences : CMLS - September 17, 2019 Category: Cytology Authors: Christofides A, Papagregoriou G, Dweep H, Makrides N, Gretz N, Felekkis K, Deltas C Tags: Cell Mol Life Sci Source Type: research

What is strain in neurodegenerative diseases?
Abstract Neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease, are characterized by the aggregation of misfolded proteins, including Aβ, tau and α-synuclein. It is well recognized that these misfolded proteins are able to self-propagate and spread throughout the nervous system and cause neuronal injury in a way that resembles prion disease. These disease-specific misfolded proteins demonstrate unique features, including the seeding barrier, the conformational memory effect, strain selection and strain evolution, based on the presence of various strains. However, the accurate d...
Source: Cellular and Molecular Life Sciences : CMLS - September 17, 2019 Category: Cytology Authors: Tian Y, Meng L, Zhang Z Tags: Cell Mol Life Sci Source Type: research

Current perspective on the regulation of FOXO4 and its role in disease progression.
Abstract Forkhead box O4 (FOXO4) is a member of the FOXO family that regulates a number of genes involved in metabolism, cell cycle, apoptosis, and cellular homeostasis via transcriptional activity. It also mediates cell responses to oxidative stress and treatment with antitumor agents. The expression of FOXO4 is repressed by microRNAs in multiple cancer cells, while FOXO4 function is regulated by post-translational modifications and interaction with other proteins. The deregulation of FOXO4 is closely linked to the progression of several types of cancer, senescence, and other diseases. In this review, we present ...
Source: Cellular and Molecular Life Sciences : CMLS - September 16, 2019 Category: Cytology Authors: Liu W, Li Y, Luo B Tags: Cell Mol Life Sci Source Type: research

Auditory function and dysfunction: estrogen makes a difference.
oix L Abstract Estrogen is the major female hormone involved in reproductive functions, but it also exerts a variety of additional roles in non-reproductive organs. In this review, we highlight the preclinical and clinical studies that have pointed out sex differences and estrogenic influence on audition. We also describe the experimental evidences supporting a protective role of estrogen towards acquired forms of hearing loss. Although a high level of endogenous estrogen is associated with a better hearing function, hormonal treatments at menopause have provided contradictory outcomes. The various factors that ar...
Source: Cellular and Molecular Life Sciences : CMLS - September 14, 2019 Category: Cytology Authors: Delhez A, Lefebvre P, Péqueux C, Malgrange B, Delacroix L Tags: Cell Mol Life Sci Source Type: research

Histone demethylase KDM4A regulates adipogenic and osteogenic differentiation via epigenetic regulation of C/EBP α and canonical Wnt signaling.
Histone demethylase KDM4A regulates adipogenic and osteogenic differentiation via epigenetic regulation of C/EBPα and canonical Wnt signaling. Cell Mol Life Sci. 2019 Sep 12;: Authors: Qi Q, Wang Y, Wang X, Yang J, Xie Y, Zhou J, Li X, Wang B Abstract Epigenetic modifications play a central role in cell differentiation and development. In the current study, we have recognized lysine demethylase 4A (KDM4A) as a novel epigenetic regulator of osteoblast and adipocyte differentiation. Kdm4a expression was upregulated during osteogenesis and adipogenesis of primary marrow stromal cells and establishe...
Source: Cellular and Molecular Life Sciences : CMLS - September 12, 2019 Category: Cytology Authors: Qi Q, Wang Y, Wang X, Yang J, Xie Y, Zhou J, Li X, Wang B Tags: Cell Mol Life Sci Source Type: research

Regulation of gap junction intercellular communication by connexin ubiquitination: physiological and pathophysiological implications.
Abstract Gap junctions consist of arrays of intercellular channels that enable adjacent cells to communicate both electrically and metabolically. Gap junctions have a wide diversity of physiological functions, playing critical roles in both excitable and non-excitable tissues. Gap junction channels are formed by integral membrane proteins called connexins. Inherited or acquired alterations in connexins are associated with numerous diseases, including heart failure, neuropathologies, deafness, skin disorders, cataracts and cancer. Gap junctions are highly dynamic structures and by modulating the turnover rate of co...
Source: Cellular and Molecular Life Sciences : CMLS - September 9, 2019 Category: Cytology Authors: Totland MZ, Rasmussen NL, Knudsen LM, Leithe E Tags: Cell Mol Life Sci Source Type: research

Toxoplasma gondii ROP16 kinase silences the cyclin B1 gene promoter by hijacking host cell UHRF1-dependent epigenetic pathways.
This study demonstrates that Toxoplasma hijacks a new epigenetic initiator, UHRF1, through an early event initiated by the ROP16 parasite kinase. PMID: 31492965 [PubMed - as supplied by publisher] (Source: Cellular and Molecular Life Sciences : CMLS)
Source: Cellular and Molecular Life Sciences : CMLS - September 6, 2019 Category: Cytology Authors: Sabou M, Doderer-Lang C, Leyer C, Konjic A, Kubina S, Lennon S, Rohr O, Viville S, Cianférani S, Candolfi E, Pfaff AW, Brunet J Tags: Cell Mol Life Sci Source Type: research

The CRL4-DCAF13 ubiquitin E3 ligase supports oocyte meiotic resumption by targeting PTEN degradation.
In this study, we demonstrated that DCAF13 stimulates the meiotic resumption-coupled activation of protein synthesis in oocytes, partially by maintaining the activity of PI3K signaling pathway. CRL4-DCAF13 targets the polyubiquitination and degradation of PTEN, a lipid phosphatase that inhibits PI3K pathway as well as oocyte growth and maturation. Dcaf13 knockout in oocytes caused decreased CDK1 activity and impaired meiotic cell cycle progression and chromosome condensation defects. As a result, chromosomes fail to be aligned at the spindle equatorial plate, the spindle assembly checkpoint is activated, and most Dcaf13 nu...
Source: Cellular and Molecular Life Sciences : CMLS - September 6, 2019 Category: Cytology Authors: Zhang J, Zhang YL, Zhao LW, Pi SB, Zhang SY, Tong C, Fan HY Tags: Cell Mol Life Sci Source Type: research

Stoichiometry and regulation network of Bcl-2 family complexes quantified by live-cell FRET assay.
Abstract The stoichiometry and affinity of Bcl-2 family complexes are essential information for understanding how their interactome network is orchestrated to regulate mitochondrial permeabilization and apoptosis. Based on over-expression model system, FRET analysis was used to quantify the protein-protein interactions among Bax, Bcl-xL, Bad and tBid in healthy and apoptotic cells. Our data indicate that the stoichiometry and affinity of Bcl-2 complexes are dependent on their membrane environment. Bcl-xL, Bad and tBid can form hetero-trimers in mitochondria. Bcl-xL binds preferentially to Bad, then to tBid and Bax...
Source: Cellular and Molecular Life Sciences : CMLS - September 6, 2019 Category: Cytology Authors: Yang F, Qu W, Du M, Mai Z, Wang B, Ma Y, Wang X, Chen T Tags: Cell Mol Life Sci Source Type: research

MicroRNA-24-3p regulates neuronal differentiation by controlling hippocalcin expression.
Abstract Hippocalcin (HPCA) is a neuron-specific calcium-binding protein predominantly expressed in the nervous system. In the present study, we demonstrate that HPCA regulates neuronal differentiation in SH-SY5Y cells. We observed that the expression level of HPCA was increased during neuronal differentiation. Depletion of HPCA inhibited both neurite outgrowth and synaptophysin (SYP) expression, whereas overexpression of HPCA enhanced neuronal differentiation. Interestingly, we also found that the expression of HPCA mRNA was modulated by miR-24-3p. Using a dual-luciferase assay, we showed that co-transfection of ...
Source: Cellular and Molecular Life Sciences : CMLS - September 5, 2019 Category: Cytology Authors: Kang MJ, Park SY, Han JS Tags: Cell Mol Life Sci Source Type: research

Structural and functional analysis of "non-smelly" proteins.
Structural and functional analysis of "non-smelly" proteins. Cell Mol Life Sci. 2019 Sep 05;: Authors: Yan J, Cheng J, Kurgan L, Uversky VN Abstract Cysteine and aromatic residues are major structure-promoting residues. We assessed the abundance, structural coverage, and functional characteristics of the "non-smelly" proteins, i.e., proteins that do not contain cysteine residues (C-depleted) or cysteine and aromatic residues (CFYWH-depleted), across 817 proteomes from all domains of life. The analysis revealed that although these proteomes contained significant levels of the C-depl...
Source: Cellular and Molecular Life Sciences : CMLS - September 5, 2019 Category: Cytology Authors: Yan J, Cheng J, Kurgan L, Uversky VN Tags: Cell Mol Life Sci Source Type: research

Sialic acid-binding immunoglobulin-like lectins (Siglecs) detect self-associated molecular patterns to regulate immune responses.
i A Abstract The mammalian immune system evolved to tightly regulate the elimination of pathogenic microbes and neoplastic transformed cells while tolerating our own healthy cells. Here, we summarize experimental evidence for the role of Siglecs-in particular CD33-related Siglecs-as self-receptors and their sialoglycan ligands in regulating this balance between recognition of self and non-self. Sialoglycans are found in the glycocalyx and extracellular fluids and matrices of all mammalian cells and can be considered as self-associated molecular patterns (SAMPs). We also provide an overview of the known interaction...
Source: Cellular and Molecular Life Sciences : CMLS - September 4, 2019 Category: Cytology Authors: Läubli H, Varki A Tags: Cell Mol Life Sci Source Type: research

Insights from Drosophila on mitochondrial complex I.
Abstract NADH:ubiquinone oxidoreductase, more commonly referred to as mitochondrial complex I (CI), is the largest discrete enzyme of the oxidative phosphorylation system (OXPHOS). It is localized to the mitochondrial inner membrane. CI oxidizes NADH generated from the tricarboxylic acid cycle to NAD+, in a series of redox reactions that culminates in the reduction of ubiquinone, and the transport of protons from the matrix across the inner membrane to the intermembrane space. The resulting proton-motive force is consumed by ATP synthase to generate ATP, or harnessed to transport ions, metabolites and proteins int...
Source: Cellular and Molecular Life Sciences : CMLS - September 4, 2019 Category: Cytology Authors: Rhooms SK, Murari A, Goparaju NSV, Vilanueva M, Owusu-Ansah E Tags: Cell Mol Life Sci Source Type: research

Knockdown of Foxg1 in supporting cells increases the trans-differentiation of supporting cells into hair cells in the neonatal mouse cochlea.
Abstract Foxg1 is one of the forkhead box genes that are involved in morphogenesis, cell fate determination, and proliferation, and Foxg1 was previously reported to be required for morphogenesis of the mammalian inner ear. However, Foxg1 knock-out mice die at birth, and thus the role of Foxg1 in regulating hair cell (HC) regeneration after birth remains unclear. Here we used Sox2CreER/+ Foxg1loxp/loxp mice and Lgr5-EGFPCreER/+ Foxg1loxp/loxp mice to conditionally knock down Foxg1 specifically in Sox2+ SCs and Lgr5+ progenitors, respectively, in neonatal mice. We found that Foxg1 conditional knockdown (cKD) in Sox2...
Source: Cellular and Molecular Life Sciences : CMLS - September 4, 2019 Category: Cytology Authors: Zhang S, Zhang Y, Dong Y, Guo L, Zhang Z, Shao B, Qi J, Zhou H, Zhu W, Yan X, Hong G, Zhang L, Zhang X, Tang M, Zhao C, Gao X, Chai R Tags: Cell Mol Life Sci Source Type: research

Group 1 metabotropic glutamate receptors trigger glutamate-induced intracellular Ca2+ signals and nitric oxide release in human brain microvascular endothelial cells.
Abstract Neurovascular coupling (NVC) is the mechanism whereby an increase in neuronal activity causes an increase in local cerebral blood flow (CBF) to ensure local supply of oxygen and nutrients to the activated areas. The excitatory neurotransmitter glutamate gates post-synaptic N-methyl-D-aspartate receptors to mediate extracellular Ca2+ entry and stimulate neuronal nitric oxide (NO) synthase to release NO, thereby triggering NVC. Recent work suggested that endothelial Ca2+ signals could underpin NVC by recruiting the endothelial NO synthase. For instance, acetylcholine induced intracellular Ca2+ signals follo...
Source: Cellular and Molecular Life Sciences : CMLS - August 31, 2019 Category: Cytology Authors: Negri S, Faris P, Pellavio G, Botta L, Orgiu M, Forcaia G, Sancini G, Laforenza U, Moccia F Tags: Cell Mol Life Sci Source Type: research

Apolipoprotein E-mediated regulation of selenoprotein P transportation via exosomes.
Abstract Selenoprotein P (SELENOP), secreted from the liver, functions as a selenium (Se) supplier to other tissues. In the brain, Se homeostasis is critical for physiological function. Previous studies have reported that SELENOP co-localizes with the apolipoprotein E receptor 2 (ApoER2) along the blood-brain barrier (BBB). However, the mechanism underlying SELENOP transportation from hepatocytes to neuronal cells remains unclear. Here, we found that SELENOP was secreted from hepatocytes as an exosomal component protected from plasma kallikrein-mediated cleavage. SELENOP was interacted with apolipoprotein E (ApoE)...
Source: Cellular and Molecular Life Sciences : CMLS - August 30, 2019 Category: Cytology Authors: Jin Y, Chung YW, Jung MK, Lee JH, Ko KY, Jang JK, Ham M, Kang H, Pack CG, Mihara H, Kim IY Tags: Cell Mol Life Sci Source Type: research

Mechanisms of resistance to estrogen receptor modulators in ER+/HER2- advanced breast cancer.
Abstract Endocrine therapy represents a mainstay adjuvant treatment of estrogen receptor-positive (ER+) breast cancer in clinical practice with an overall survival (OS) benefit. However, the emergence of resistance is inevitable over time and is present in one-third of the ER+ breast tumors. Several mechanisms of endocrine resistance in ER+/HER2- advanced breast cancers, through ERα itself, receptor tyrosine signaling, or cell cycle pathway, have been identified to be pivotal in endocrine therapy. The epigenetic alterations also contribute to ensuring tumor cells' escape from endocrine therapie...
Source: Cellular and Molecular Life Sciences : CMLS - August 30, 2019 Category: Cytology Authors: Zhang J, Wang Q, Wang Q, Cao J, Sun J, Zhu Z Tags: Cell Mol Life Sci Source Type: research

Placental mesenchymal stromal cells as an alternative tool for therapeutic angiogenesis.
Abstract Dysregulation of angiogenesis is a phenomenon observed in several disorders such as diabetic foot, critical limb ischemia and myocardial infarction. Mesenchymal stromal cells (MSCs) possess angiogenic potential and have recently emerged as a powerful tool for cell therapy to promote angiogenesis. Although bone marrow-derived MSCs are the primary cell of choice, obtaining them has become a challenge. The placenta has become a popular alternative as it is a highly vascular organ, easily available and ethically more favorable with a rich supply of MSCs. Comparatively, placenta-derived MSCs (PMSCs) are clinic...
Source: Cellular and Molecular Life Sciences : CMLS - August 29, 2019 Category: Cytology Authors: Mathew SA, Naik C, Cahill PA, Bhonde RR Tags: Cell Mol Life Sci Source Type: research

Drug repurposing studies of PARP inhibitors as a new therapy for inherited retinal degeneration.
Abstract The enzyme poly-ADP-ribose-polymerase (PARP) has important roles for many forms of DNA repair and it also participates in transcription, chromatin remodeling and cell death signaling. Currently, some PARP inhibitors are approved for cancer therapy, by means of canceling DNA repair processes and cell division. Drug repurposing is a new and attractive aspect of therapy development that could offer low-cost and accelerated establishment of new treatment options. Excessive PARP activity is also involved in neurodegenerative diseases including the currently untreatable and blinding retinitis pigmentosa group o...
Source: Cellular and Molecular Life Sciences : CMLS - August 26, 2019 Category: Cytology Authors: Sahaboglu A, Miranda M, Canjuga D, Avci-Adali M, Savytska N, Secer E, Feria-Pliego JA, Kayık G, Durdagi S Tags: Cell Mol Life Sci Source Type: research

Tetraspanin1 promotes NGF signaling by controlling TrkA receptor proteostasis.
Abstract The molecular mechanisms that control the biosynthetic trafficking, surface delivery, and degradation of TrkA receptor are essential for proper nerve growth factor (NGF) function, and remain poorly understood. Here, we identify Tetraspanin1 (Tspan1) as a critical regulator of TrkA signaling and neuronal differentiation induced by NGF. Tspan1 is expressed by developing TrkA-positive dorsal root ganglion (DRG) neurons and its downregulation in sensory neurons inhibits NGF-mediated axonal growth. In addition, our data demonstrate that Tspan1 forms a molecular complex with the immature form of TrkA localized ...
Source: Cellular and Molecular Life Sciences : CMLS - August 22, 2019 Category: Cytology Authors: Ferrero Restelli F, Fontanet PA, De Vincenti AP, Falzone TL, Ledda F, Paratcha G Tags: Cell Mol Life Sci Source Type: research

Copper-mediated thiol potentiation and mutagenesis-guided modeling suggest a highly conserved copper-binding motif in human OR2M3.
Abstract Sulfur-containing compounds within a physiological relevant, natural odor space, such as the key food odorants, typically constitute the group of volatiles with the lowest odor thresholds. The observation that certain metals, such as copper, potentiate the smell of sulfur-containing, metal-coordinating odorants led to the hypothesis that their cognate receptors are metalloproteins. However, experimental evidence is sparse-so far, only one human odorant receptor, OR2T11, and a few mouse receptors, have been reported to be activated by sulfur-containing odorants in a copper-dependent way, while the activati...
Source: Cellular and Molecular Life Sciences : CMLS - August 21, 2019 Category: Cytology Authors: Haag F, Ahmed L, Reiss K, Block E, Batista VS, Krautwurst D Tags: Cell Mol Life Sci Source Type: research

G-protein βγ subunits as multi-functional scaffolds and transducers in G-protein-coupled receptor signaling.
G-protein βγ subunits as multi-functional scaffolds and transducers in G-protein-coupled receptor signaling. Cell Mol Life Sci. 2019 Aug 21;: Authors: Smrcka AV, Fisher I Abstract G-protein βγ subunits are key participants in G-protein signaling. These subunits facilitate interactions between receptors and G proteins that are critical for the G protein activation cycle at the plasma membrane. In addition, they play roles in directly transducing signals to an ever expanding range of downstream targets, including integral membrane and cytosolic proteins. Emerging data indicate that...
Source: Cellular and Molecular Life Sciences : CMLS - August 21, 2019 Category: Cytology Authors: Smrcka AV, Fisher I Tags: Cell Mol Life Sci Source Type: research

The enhancement of glycolysis regulates pancreatic cancer metastasis.
Abstract Pancreatic ductal adenocarcinoma is prone to distant metastasis and is expected to become the second leading cause of cancer-related death. In an extremely nutrient-deficient and hypoxic environment resulting from uncontrolled growth, vascular disturbances and desmoplastic reactions, pancreatic cancer cells utilize "metabolic reprogramming" to satisfy their energy demand and support malignant behaviors such as metastasis. Notably, pancreatic cancer cells show extensive enhancement of glycolysis, including glycolytic enzyme overexpression and increased lactate production, and this is caused by mi...
Source: Cellular and Molecular Life Sciences : CMLS - August 20, 2019 Category: Cytology Authors: Yang J, Ren B, Yang G, Wang H, Chen G, You L, Zhang T, Zhao Y Tags: Cell Mol Life Sci Source Type: research

Insights into the mechanisms of epilepsy from structural biology of LGI1-ADAM22.
Abstract Epilepsy is one of the most common brain disorders, which can be caused by abnormal synaptic transmissions. Many epilepsy-related mutations have been identified in synaptic ion channels, which are main targets for current antiepileptic drugs. One of the novel potential targets for therapy of epilepsy is a class of non-ion channel-type epilepsy-related proteins. The leucine-rich repeat glioma-inactivated protein 1 (LGI1) is a neuronal secreted protein, and has been extensively studied as a product of a causative gene for autosomal dominant lateral temporal lobe epilepsy (ADLTE; also known as autosomal domi...
Source: Cellular and Molecular Life Sciences : CMLS - August 20, 2019 Category: Cytology Authors: Yamagata A, Fukai S Tags: Cell Mol Life Sci Source Type: research

G protein-coupled receptor kinase 2 (GRK2) as a multifunctional signaling hub.
yor F Abstract Accumulating evidence indicates that G protein-coupled receptor kinase 2 (GRK2) is a versatile protein that acts as a signaling hub by modulating G protein-coupled receptor (GPCR) signaling and also via phosphorylation or scaffolding interactions with an extensive number of non-GPCR cellular partners. GRK2 multifunctionality arises from its multidomain structure and from complex mechanisms of regulation of its expression levels, activity, and localization within the cell, what allows the precise spatio-temporal shaping of GRK2 targets. A better understanding of the GRK2 interactome and its modulatio...
Source: Cellular and Molecular Life Sciences : CMLS - August 20, 2019 Category: Cytology Authors: Penela P, Ribas C, Sánchez-Madrid F, Mayor F Tags: Cell Mol Life Sci Source Type: research

Understanding protein multifunctionality: from short linear motifs to cellular functions.
Abstract Moonlighting proteins perform multiple unrelated functions without any change in polypeptide sequence. They can coordinate cellular activities, serving as switches between pathways and helping to respond to changes in the cellular environment. Therefore, regulation of the multiple protein activities, in space and time, is likely to be important for the homeostasis of biological systems. Some moonlighting proteins may perform their multiple functions simultaneously while others alternate between functions due to certain triggers. The switch of the moonlighting protein's functions can be regulated by severa...
Source: Cellular and Molecular Life Sciences : CMLS - August 20, 2019 Category: Cytology Authors: Zanzoni A, Ribeiro DM, Brun C Tags: Cell Mol Life Sci Source Type: research

Molecular switches for regulating the differentiation of inflammatory and IL-10-producing anti-inflammatory T-helper cells.
Abstract CD4 T-helper (Th) cells secret a variety of inflammatory cytokines and play critical roles in host defense against invading foreign pathogens. On the other hand, uncontrolled inflammatory responses mediated by Th cells may result in tissue damage and inflammatory disorders including autoimmune and allergic diseases. Thus, the induction of anti-inflammatory cytokine expression becomes an important "brake" to repress and/or terminate aberrant and/or unnecessary immune responses. Interleukin-10 (IL-10) is one of the most important anti-inflammatory cytokines to limit inflammatory Th cells and immun...
Source: Cellular and Molecular Life Sciences : CMLS - August 20, 2019 Category: Cytology Authors: Fang D, Zhu J Tags: Cell Mol Life Sci Source Type: research

Multi-functionality of proteins involved in GPCR and G protein signaling: making sense of structure-function continuum with intrinsic disorder-based proteoforms.
Abstract GPCR-G protein signaling system recognizes a multitude of extracellular ligands and triggers a variety of intracellular signaling cascades in response. In humans, this system includes more than 800 various GPCRs and a large set of heterotrimeric G proteins. Complexity of this system goes far beyond a multitude of pair-wise ligand-GPCR and GPCR-G protein interactions. In fact, one GPCR can recognize more than one extracellular signal and interact with more than one G protein. Furthermore, one ligand can activate more than one GPCR, and multiple GPCRs can couple to the same G protein. This defines an intric...
Source: Cellular and Molecular Life Sciences : CMLS - August 19, 2019 Category: Cytology Authors: Fonin AV, Darling AL, Kuznetsova IM, Turoverov KK, Uversky VN Tags: Cell Mol Life Sci Source Type: research

Organization and dynamics of functional plant membrane microdomains.
Abstract Plasma membranes are heterogeneous and laterally compartmentalized into distinct microdomains. These membrane microdomains consist of special lipids and proteins and are thought to act as signaling platforms. In plants, membrane microdomains have been detected by super-resolution microscopy, and there is evidence that they play roles in several biological processes. Here, we review current knowledge about the lipid and protein components of membrane microdomains. Furthermore, we summarize the dynamics of membrane microdomains in response to different stimuli. We also explore the biological functions assoc...
Source: Cellular and Molecular Life Sciences : CMLS - August 17, 2019 Category: Cytology Authors: Yu M, Cui Y, Zhang X, Li R, Lin J Tags: Cell Mol Life Sci Source Type: research

Protein multi-functionality: introduction.
Abstract The five articles in this multi-author review in CMLS provide examples of multi-functionality of proteins belonging to several families. Distinct structural features of proteins suggesting multi-functionality are emphasized: intrinsically disordered elements that can "mold" themselves to fit various binding partners, as well as short linear motifs within larger proteins that perform particular functions. Although only a few protein families are discussed in detail, the conclusions apply to numerous, if not all, proteins. Multi-functionality of virtually every protein implies that the manipulatio...
Source: Cellular and Molecular Life Sciences : CMLS - August 17, 2019 Category: Cytology Authors: Gurevich VV Tags: Cell Mol Life Sci Source Type: research

Plethora of functions packed into 45  kDa arrestins: biological implications and possible therapeutic strategies.
Plethora of functions packed into 45 kDa arrestins: biological implications and possible therapeutic strategies. Cell Mol Life Sci. 2019 Aug 17;: Authors: Gurevich VV, Gurevich EV Abstract Mammalian arrestins are a family of four highly homologous relatively small ~ 45 kDa proteins with surprisingly diverse functions. The most striking feature is that each of the two non-visual subtypes can bind hundreds of diverse G protein-coupled receptors (GPCRs) and dozens of non-receptor partners. Through these interactions, arrestins regulate the G protein-dependent signaling by the dese...
Source: Cellular and Molecular Life Sciences : CMLS - August 17, 2019 Category: Cytology Authors: Gurevich VV, Gurevich EV Tags: Cell Mol Life Sci Source Type: research

Atypical cyclins: the extended family portrait.
Abstract Regulation of cell division is orchestrated by cyclins, which bind and activate their catalytic workmates, the cyclin-dependent kinases (CDKs). Cyclins have been traditionally defined by an oscillating (cyclic) pattern of expression and by the presence of a characteristic "cyclin box" that determines binding to the CDKs. Noteworthy, the Human Genome Sequence Project unveiled the existence of several other proteins containing the "cyclin box" domain. These potential "cyclins" have been named new, orphan or atypical, creating a conundrum in cyclins nomenclature. Moreover, altho...
Source: Cellular and Molecular Life Sciences : CMLS - August 16, 2019 Category: Cytology Authors: Quandt E, Ribeiro MPC, Clotet J Tags: Cell Mol Life Sci Source Type: research

Mechanisms and significance of therapy-induced and spontaneous senescence of cancer cells.
Abstract In contrast to the well-recognized replicative and stress-induced premature senescence of normal somatic cells, mechanisms and clinical implications of senescence of cancer cells are still elusive and uncertain from patient-oriented perspective. Moreover, recent years provided multiple pieces of evidence that cancer cells may undergo senescence not only in response to chemotherapy or ionizing radiation (the so-called therapy-induced senescence) but also spontaneously, without any external insults. Since the molecular nature of the latter process is poorly recognized, the significance of spontaneously sene...
Source: Cellular and Molecular Life Sciences : CMLS - August 14, 2019 Category: Cytology Authors: Mikuła-Pietrasik J, Niklas A, Uruski P, Tykarski A, Książek K Tags: Cell Mol Life Sci Source Type: research

Farnesoid X receptor alpha (FXR α) is a critical actor of the development and pathologies of the male reproductive system.
Farnesoid X receptor alpha (FXRα) is a critical actor of the development and pathologies of the male reproductive system. Cell Mol Life Sci. 2019 Aug 12;: Authors: Garcia M, Thirouard L, Monrose M, Holota H, De Haze A, Caira F, Beaudoin C, Volle DH Abstract The farnesoid-X-receptorα (FXRα; NR1H4) is one of the main bile acid (BA) receptors. During the last decades, through the use of pharmalogical approaches and transgenic mouse models, it has been demonstrated that the nuclear receptor FXRα controls numerous physiological functions such as glucose or energy metabolisms. I...
Source: Cellular and Molecular Life Sciences : CMLS - August 12, 2019 Category: Cytology Authors: Garcia M, Thirouard L, Monrose M, Holota H, De Haze A, Caira F, Beaudoin C, Volle DH Tags: Cell Mol Life Sci Source Type: research

Smad linker region phosphorylation is a signalling pathway in its own right and not only a modulator of canonical TGF- β signalling.
Smad linker region phosphorylation is a signalling pathway in its own right and not only a modulator of canonical TGF-β signalling. Cell Mol Life Sci. 2019 Aug 12;: Authors: Kamato D, Do BH, Osman N, Ross BP, Mohamed R, Xu S, Little PJ Abstract Transforming growth factor (TGF)-β signalling pathways are intensively investigated because of their diverse association with physiological and pathophysiological states. Smad transcription factors are the key mediators of TGF-β signalling. Smads can be directly phosphorylated in the carboxy terminal by the TGF-β receptor or in the linker re...
Source: Cellular and Molecular Life Sciences : CMLS - August 12, 2019 Category: Cytology Authors: Kamato D, Do BH, Osman N, Ross BP, Mohamed R, Xu S, Little PJ Tags: Cell Mol Life Sci Source Type: research

Compensatory increase of VE-cadherin expression through ETS1 regulates endothelial barrier function in response to TNF α.
Compensatory increase of VE-cadherin expression through ETS1 regulates endothelial barrier function in response to TNFα. Cell Mol Life Sci. 2019 Aug 08;: Authors: Colás-Algora N, García-Weber D, Cacho-Navas C, Barroso S, Caballero A, Ribas C, Correas I, Millán J Abstract VE-cadherin plays a central role in controlling endothelial barrier function, which is transiently disrupted by proinflammatory cytokines such as tumor necrosis factor (TNFα). Here we show that human endothelial cells compensate VE-cadherin degradation in response to TNFα by inducing VE-cadherin ...
Source: Cellular and Molecular Life Sciences : CMLS - August 8, 2019 Category: Cytology Authors: Colás-Algora N, García-Weber D, Cacho-Navas C, Barroso S, Caballero A, Ribas C, Correas I, Millán J Tags: Cell Mol Life Sci Source Type: research