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A light-driven sodium ion pump in marine bacteria
Light-driven proton-pumping rhodopsins are widely distributed in microorganisms and convert sunlight energy into proton gradients. Inoue et al. report the discovery of a light-driven sodium ion pump from marine bacteria.
- Keiichi Inoue
- , Hikaru Ono
- & Hideki Kandori
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Regulation of NF-κB signalling by the mono-ADP-ribosyltransferase ARTD10
Mono-ADP-ribosylation is a recently discovered post-translational modification whose function remains unclear. Verheugd et al. show that the mono-ADP-ribosyltransferase ARTD10 inhibits NF-κB activation by preventing the poly-ubiquitination of NEMO, suggesting a functional link between these two modifications.
- Patricia Verheugd
- , Alexandra H. Forst
- & Bernhard Lüscher
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| Open AccessCSN- and CAND1-dependent remodelling of the budding yeast SCF complex
CAND1 promotes the activity of Cullin–RING ubiquitin ligases, but binds exclusively to inactive unneddylated forms of the enzyme. By identifying a simple means to reversibly activate this complex in budding yeast, Zemla et al. resolve this paradox and show that CAND1 acts as an exchange factor for substrate adaptors.
- Aleksandra Zemla
- , Yann Thomas
- & Thimo Kurz
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CAND1 controls in vivo dynamics of the cullin 1-RING ubiquitin ligase repertoire
Cullin 1-RING ubiquitin ligase complexes interact with a wide variety of substrates by recruiting different substrate receptor subunits. Here the authors demonstrate that CAND1 promotes rapid exchange of substrate receptors, thus ensuring comprehensive sampling of the entire repertoire.
- Shuangding Wu
- , Wenhong Zhu
- & Dieter A. Wolf
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| Open AccessTopoisomerase IIα promotes activation of RNA polymerase I transcription by facilitating pre-initiation complex formation
Topoisomerases facilitate the progress of elongating polymerases during transcription. Zomerdijk and colleagues now demonstrate an additional role for this enzyme; their data suggest that Top2 can cleave DNA inducing topological changes at the ribosomal DNA promoter, which assists de novoassembly of the RNA polymerase I pre-initiation complex.
- Swagat Ray
- , Tatiana Panova
- & Joost C. B. M. Zomerdijk
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Crystal structure of human tyrosylprotein sulfotransferase-2 reveals the mechanism of protein tyrosine sulfation reaction
The post-translational protein modification tyrosine sulfation is catalysed by tyrosylprotein sulfotransferase (TPST). Teramoto et al. present the first crystal structure of the human TPST isoform 2 complexed with a substrate peptide derived from complement C4 and 3′phosphoadenosine-5′-phosphate, revealing the molecular basis of catalysis.
- Takamasa Teramoto
- , Yukari Fujikawa
- & Yoshimitsu Kakuta
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| Open AccessThe transcriptional repressor NKAP is required for the development of iNKT cells
The transcriptional repressor NKAP is required at an early stage of T cell development for the differentiation of αβ T cells. Thapa et al.now show that at a later stage, NKAP has a specific role in positive selection of double positive thymocytes into the iNKT cell lineage.
- Puspa Thapa
- , Joy Das
- & Virginia Smith Shapiro
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| Open AccessReversible inactivation of deubiquitinases by reactive oxygen species in vitro and in cells
Deubiquitinases regulate protein stability, localization and activity, and yet the mechanisms controlling their activity remain poorly understood. Lee et al. show that these enzymes are reversibly inhibited by reactive oxygen species through oxidation of catalytic cysteine residues.
- Jin-Gu Lee
- , Kheewoong Baek
- & Yihong Ye
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Regulation of A20 and other OTU deubiquitinases by reversible oxidation
Ovarian tumour deubiquitinases are cysteine proteases that cleave polyubiquitin chains. Here the authors show that these enzymes are susceptible to reversible oxidation, and present crystal structures which reveal how the reversibly oxidized catalytic cysteine residue is stabilized by the active site.
- Yogesh Kulathu
- , Francisco J. Garcia
- & David Komander
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COG complexes form spatial landmarks for distinct SNARE complexes
COG complexes are thought to be involved in tethering of intra-Golgi vesicles. Here the authors show that individual COG complex subunits direct the assembly of distinct vesicle-tethering platforms, suggesting that COG subunits have a role in the specificity of vesicular sorting.
- Rose Willett
- , Tetyana Kudlyk
- & Vladimir Lupashin
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Siva1 inhibits p53 function by acting as an ARF E3 ubiquitin ligase
The proapoptotic protein Siva1 has been shown to inhibit the tumour suppressor p53, however, it remains unclear how this activity is mediated. Here the authors show that Siva1 is an E3 ubiquitin ligase which inhibits p53 by promoting the degradation of ARF.
- Xingwu Wang
- , Meng Zha
- & Mian Wu
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| Open AccessGreater efficiency of photosynthetic carbon fixation due to single amino-acid substitution
Phosphoenolpyruvate carboxylase, the key enzyme of C4 photosynthesis, evolved from an ancestral isoform in C3 plants and has a reduced feedback inhibition. Paulus et al.show that enhanced inhibitor tolerance of C4 phosphoenolpyruvate carboxylase is achieved by a single amino-acid exchange.
- Judith Katharina Paulus
- , Daniel Schlieper
- & Georg Groth
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De novo lipogenesis in human fat and liver is linked to ChREBP-β and metabolic health
Changes in the biosynthesis of fatty acids can influence tissue insulin sensitivity and the development of metabolic diseases. Eissing and colleagues show that de novolipogenesis in liver and adipose tissue is linked to metabolic health in humans and can be modulated by bariatric surgery.
- Leah Eissing
- , Thomas Scherer
- & Ludger Scheja
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| Open AccessA new class of plant lipid is essential for protection against phosphorus depletion
Phosphorus supply is one of the major factors responsible for reduced crop yields. Here Okazaki et al.use untargeted lipidomics to elucidate the biosynthetic pathway of a novel plant lipid, glucuronosyldiacylglycerol, which is essential for the protection of plants against phosphorus depletion.
- Yozo Okazaki
- , Hitomi Otsuki
- & Kazuki Saito
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Enhanced dihydropyridine receptor calcium channel activity restores muscle strength in JP45/CASQ1 double knockout mice
Calcium influx through the Cav1.1 channel initiates skeletal muscle contractions. Zorzato and colleagues report a role for the proteins JP45 and calsequestrin in strengthening skeletal muscle contraction by modulating Cav1.1 channel activity.
- Barbara Mosca
- , Osvaldo Delbono
- & Francesco Zorzato
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| Open AccessDisease mutations in the ryanodine receptor N-terminal region couple to a mobile intersubunit interface
Ryanodine receptors are calcium-release channels located in the membrane of the sarcoplasmic and endoplasmic reticulum. Kimlicka et al.compare pseudo-atomic models of the N-terminal area in the open and closed states and characterize the mutations in the N-terminal that disrupt channel opening.
- Lynn Kimlicka
- , Kelvin Lau
- & Filip Van Petegem
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| Open AccessCell wall elongation mode in Gram-negative bacteria is determined by peptidoglycan architecture
Bacterial cell wall peptidoglycan is essential for viability and shape determination. Using high-resolution microscopy, Foster and colleagues elucidate the peptidoglycan architecture and insertion pattern in Escherichia coliand other Gram-negative bacteria, and propose a new model for cell wall elongation.
- Robert D. Turner
- , Alexander F. Hurd
- & Simon J. Foster
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Mechanism of tetracycline resistance by ribosomal protection protein Tet(O)
The bacterial tetracycline resistance protein Tet(O) binds to the ribosome, preventing tetracycline from inhibiting translation. Using cryo-electron microscopic reconstruction, the authors present an atomic model of Tet(O) bound to the 70S ribosome, and reveal how Tet(O) promotes antibiotic resistance.
- Wen Li
- , Gemma C. Atkinson
- & Joachim Frank
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Ground-state proton transfer in the photoswitching reactions of the fluorescent protein Dronpa
The ‘on’ and ‘off’ states of the photoswitchable protein Dronpa have been characterized, but the interconversion process remains poorly understood. Here the authors perform time-resolved ultrafast infrared measurements to follow both the structural changes and proton transfer events that occur during conversion.
- Mark M. Warren
- , Marius Kaucikas
- & Jasper J. van Thor
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| Open AccessHuman CLPP reverts the longevity phenotype of a fungal ClpP deletion strain
The mitochondrial protease CLPP is found in most eukaryotic organisms but its biological role has been unclear. Here Osiewacz and colleagues show that deletion of CLPP extends lifespan of the filamentous fungus Podospora anserina, and that human and fungal CLPP are functionally conserved.
- Fabian Fischer
- , Andrea Weil
- & Heinz D. Osiewacz
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Deep proteome profiling of Trichoplax adhaerens reveals remarkable features at the origin of metazoan multicellularity
Trichoplaxis the most primitive multicellular animal on Earth and thus provides insight into the earliest stages of evolution. Delving deep into the proteome, Heck and colleagues observe a burst in tyrosine phosphorylation, confirming the hypothesis that at the onset of this new communication system a surplus of phosphorylation took place.
- Jeffrey H. Ringrose
- , Henk W.P. van den Toorn
- & Albert J.R. Heck
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Heat shock factor-1 influences pathological lesion distribution of polyglutamine-induced neurodegeneration
Heat shock factor-1 is a transcriptional regulator of heat shock proteins that is implicated in neurodegeneration. Kondo and colleagues study the effects of deleting heat shock factor-1 in a mouse model of muscular dystrophy and find that this augments the condition via the accumulation of androgen receptors.
- Naohide Kondo
- , Masahisa Katsuno
- & Gen Sobue
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Modular optimization of multi-gene pathways for fatty acids production in E. coli
Microbial fatty acid-derived fuels represent promising alternatives to the traditionally used fossil fuels. Koffas and colleagues report that E. colicentral metabolism can be modified to produce large quantities of fatty acids through a modular pathway engineering strategy.
- Peng Xu
- , Qin Gu
- & Mattheos A.G. Koffas
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A novel pathway for the production of hydrogen sulfide from D-cysteine in mammalian cells
Hydrogen sulphide is a signalling molecule with cytoprotective activity in mammals. Here, Kimura and colleagues identify a new biosynthetic pathway for the production of hydrogen sulphide from D-cysteine, which is shown to protect mouse kidneys from oxidative stress after ischaemia/reperfusion injury.
- Norihiro Shibuya
- , Shin Koike
- & Hideo Kimura
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| Open AccessMultiple pore conformations driven by asynchronous movements of voltage sensors in a eukaryotic sodium channel
In outwardly rectifying potassium channels, depolarization initiates conformational changes in voltage-sensing domains. Goldschen-Ohmet al. find that movement of three specific domains correlates with conductance levels, and rearrangements of a fourth domain results in preinactivation subconductance states.
- Marcel P. Goldschen-Ohm
- , Deborah L. Capes
- & Baron Chanda
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hVps41 and VAMP7 function in direct TGN to late endosome transport of lysosomal membrane proteins
Delivery of lysosome-associated membrane proteins (LAMPs), is important for lysosome stability and function. Here, Pols et al. identify a previously uncharacterized pathway for transport of lysosome-associated membrane proteins LAMPs directly from the trans-golgi network to late endosomes.
- Maaike S. Pols
- , Eline van Meel
- & Judith Klumperman
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| Open AccessStructural insights into protein-only RNase P complexed with tRNA
RNase P is a key enzyme implicated in transfer RNA maturation that removes the 5′-leader sequences from transfer RNA precursors. In this study, a biophysical characterization of a novel protein-only variant of RNase P, known as PRORP (PROteinaceous RNase P), reveals that transfer RNA recognition by PRORP is similar to that by ribonucleoprotein RNase P.
- Anthony Gobert
- , Franziska Pinker
- & Philippe Giegé
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| Open AccessAlba shapes the archaeal genome using a delicate balance of bridging and stiffening the DNA
How the genome is physically organized is less understood in archaea than in eubacteria or eukaryotes. Laurens et al. measure DNA binding by the Sulfolobus solfataricusproteins Alba1 and Alba2 using single-molecule techniques and conclude that the presence of Alba2 leads to more bridging between DNA.
- Niels Laurens
- , Rosalie P.C. Driessen
- & Gijs J.L. Wuite
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| Open AccessExtracellular Ca2+ is a danger signal activating the NLRP3 inflammasome through G protein-coupled calcium sensing receptors
Levels of extracellular calcium can increase at sites of infection and inflammation; however, the physiological significance of this has been unclear. This work shows that extracellular calcium acts as a danger signal, triggering the NLRP3 inflammasome via two G protein-coupled receptors.
- Manuela Rossol
- , Matthias Pierer
- & Ulf Wagner
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| Open AccessProteome-wide selected reaction monitoring assays for the human pathogen Streptococcus pyogenes
Selected reaction monitoring mass spectrometry (SRM-MS) can quantify dynamic changes in protein expression with high sensitivity. Karlsson et al. define optimal detection parameters for 10,412 distinct group A Streptococcus pyogenespeptides, which facilitates proteome-wide SRM-MS studies in this bacterium.
- Christofer Karlsson
- , Lars Malmström
- & Johan Malmström
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Catalytic site remodelling of the DOT1L methyltransferase by selective inhibitors
Selective inhibitors of protein methyltransferases are anticancer drug candidates. Yu et al. report the structural changes that occur when selective inhibitors bind to the protein methyltransferase DOT1L.
- Wenyu Yu
- , Emma J. Chory
- & Matthieu Schapira
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Plasmodium falciparum heat shock protein 110 stabilizes the asparagine repeat-rich parasite proteome during malarial fevers
The proteome of the malarial parasite Plasmodium falciparum has an overabundance of aggregation-prone asparagine repeat-containing proteins. Muralidharan et al. show that PlasmodiumHsp110 protein potently prevents aggregation of asparagine-rich proteins, thereby allowing the parasite to survive febrile episodes.
- Vasant Muralidharan
- , Anna Oksman
- & Daniel E. Goldberg
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| Open AccessMPIase is a glycolipozyme essential for membrane protein integration
Proteins are integrated into cellular membranes either co-translationally through Sec/SRP or post-translationally by chaperones. These authors show that an integration-dedicated chaperone inE. coli, MPIase, is a glycolipid and facilitates protein insertion into the inner membrane of the bacterium.
- Ken-ichi Nishiyama
- , Masahide Maeda
- & Keiko Shimamoto
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Cholesterol modulates cell signaling and protein networking by specifically interacting with PDZ domain-containing scaffold proteins
Cholesterol indirectly regulates intracellular signalling by modulating the physical properties of lipid membranes. Sheng et al.now show that many PDZ domains contain a functional cholesterol-binding motif, revealing that cholesterol can also control the localization and function of signalling proteins directly.
- Ren Sheng
- , Yong Chen
- & Wonhwa Cho
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Cardioprotection by Klotho through downregulation of TRPC6 channels in the mouse heart
Mice that cannot produce the hormone Klotho show various aging-related phenotypes. Here, Xie and colleagues reveal that Klotho protects the heart of mice from stress-induced remodelling by inhibiting exocytosis of the TRPC6 ion channel in cardiomyocytes.
- Jian Xie
- , Seung-Kuy Cha
- & Chou-Long Huang
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| Open AccessIdentification and characterization of a human mitochondrial NAD kinase
Despite the central importance of NADP+ in mitochondrial energy metabolism, no NAD kinase has been found in human mitochondria to synthesize NADP+. These authors show C5orf33, a protein specific to animals and protists, to be the missing NAD kinase and demonstrate its mitochondrial localization and activity.
- Kazuto Ohashi
- , Shigeyuki Kawai
- & Kousaku Murata
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Molecular mechanism of the assembly of an acid-sensing receptor ion channel complex
Polycystic kidney disease family proteins form heteromeric complexes with transient receptor potential channel subunits of the TRPP subfamily. Yu and colleagues find that the polycystic kidney disease protein, PKD1L3, is an ion channel pore-forming subunit in the acid-sensing PKD1L3/TRPP3 complex.
- Yong Yu
- , Maximilian H. Ulbrich
- & Jian Yang
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Sub-resolution lipid domains exist in the plasma membrane and regulate protein diffusion and distribution
The plasma membrane is thought to comprise a patchwork of ordered and disordered microdomains; however, direct evidence for this in intact cells remains elusive. Using unmixing of fluorescence lifetime decays, Owen et al. show that ordered domains occupy a majority of the plasma membrane surface in living cells.
- Dylan M. Owen
- , David J. Williamson
- & Katharina Gaus
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Diminishing returns and tradeoffs constrain the laboratory optimization of an enzyme
Enzymes are traditionally viewed as being highly specific for their substrates. Tokuriki et al.follow the accumulation of mutations during the laboratory evolution of a phosphotriesterase into an arylesterase, and postulate that many naturally occurring enzymes may not be optimal for their substrates.
- Nobuhiko Tokuriki
- , Colin J. Jackson
- & Dan S. Tawfik
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| Open AccessSupporting conditional mouse mutagenesis with a comprehensive cre characterization resource
The cre-loxP system is widely used for the generation of conditional gene knockouts. Here Heffner et al.systematically characterize cre recombinase activity in tissues of embryonic and adult cre-driver mouse strains and provide an online resource for scientists.
- Caleb S. Heffner
- , C. Herbert Pratt
- & Stephen A. Murray
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Cellulose degradation and assimilation by the unicellular phototrophic eukaryote Chlamydomonas reinhardtii
Although cellulose is abundant in the biosphere, its potential as a source of biofuel depends on finding efficient ways to degrade it. Blifernez-Klassen et al. show that phototrophic microalga Chlamydomonas reinhardtiican metabolize cellulose, indicating its potential as a catalyst for biofuel production.
- Olga Blifernez-Klassen
- , Viktor Klassen
- & Olaf Kruse
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The metastasis-promoting S100A4 protein confers neuroprotection in brain injury
Multifunctional S100 proteins are upregulated in brain injury, but their role in neurodegeneration is not clear. Dmytriyeva and colleagues study in vivomodels of brain trauma and find that the S100A4 protein and its peptide mimetics protect neurons via the interleukin-10 receptor and the Janus kinase (JAK)/STAT pathway.
- Oksana Dmytriyeva
- , Stanislava Pankratova
- & Darya Kiryushko
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Structural modelling and mutant cycle analysis predict pharmacoresponsiveness of a Nav1.7 mutant channel
Mutations of the NaV1.7 voltage-gated sodium channel are implicated in abnormal pain signal transduction. Yang and colleagues perform structural modeling, mutant cycle analysis and electrophysiology on specific mutants and find that they can accurately predict their response profiles to channel blockers.
- Yang Yang
- , Sulayman D. Dib-Hajj
- & Stephen G. Waxman
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A peptide derived from laminin-γ3 reversibly impairs spermatogenesis in rats
The temporal opening and closing of cell–cell junctions at the blood–testis barrier allows the passage of immature germ cells during spermatogenesis. Su and colleagues identify a peptide fragment of the laminin-γ3 chain that disrupts the blood–testis barrier and reversibly impairs spermatogenesis in rats.
- Linlin Su
- , Dolores D. Mruk
- & C. Yan Cheng
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Engineering RNA endonucleases with customized sequence specificities
Sequence-specific DNA endonucleases have found numerous applications in biology, but similar manipulations of RNA have been limited by the lack of suitable enzymes. These authors combine a cleavage domain with a designable binding domain and demonstrate the resulting RNA endonuclease's utilityin vitroand in cells.
- Rajarshi Choudhury
- , Yihsuan S. Tsai
- & Zefeng Wang
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Imaging the post-fusion release and capture of a vesicle membrane protein
Rapid synaptic transmission requires efficient recycling of synaptic vesicle membrane proteins. Sochackiet al.use live cell, electron and super-resolution microscopy to visualize exocytosis of vesicular transporters and their rapid recapture in clathrin-rich microdomains in the plasma membrane.
- Kem A. Sochacki
- , Ben T. Larson
- & Justin W. Taraska
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The convergent evolution of defensive polyacetylenic fatty acid biosynthesis genes in soldier beetles
Soldier beetles use a polyacetylenic fatty acid to repel avian predators and protect their eggs. Haritoset al. find that three genes in soldier beetles convert oleic acid to a precursor of 8Z-dihydromatricaria acid—the first eukaryotic genes reported to produce conjugated polyacetylenic fatty acids.
- Victoria S. Haritos
- , Irene Horne
- & Mats Hamberg
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CaV1.3-selective L-type calcium channel antagonists as potential new therapeutics for Parkinson's disease
L-type calcium channels comprising the CaV1.3 subunit have been linked to the generation of mitochondrial oxidant stress in Parkinson’s disease. Kang et al. identify pyrimidine-2,4,6-triones as a potential molecular scaffold, which they modify to develop a potent and highly selective CaV1.3 antagonist.
- Soosung Kang
- , Garry Cooper
- & Richard B. Silverman
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| Open AccessPrion protein facilitates uptake of zinc into neuronal cells
Prion proteins are implicated in a range of neurodegenerative diseases, which are, in part, due to a disruption of metal homeostasis. Wattet al.use selective antagonists to show that prion proteins mediate zinc uptake by interacting with GluA2-lacking, GluA1-containing AMPA receptors.
- Nicole T. Watt
- , David R. Taylor
- & Nigel M. Hooper
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