Featured
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LGALS3BP regulates centriole biogenesis and centrosome hypertrophy in cancer cells
Dysregulation of centrosome size and number is frequently associated with cancer. Fogeron et al. construct a protein-interaction network to identify proteins that are relevant for centrosome abnormalities in cancer, and show that deregulation of LGALS3BP affects centrosomal biogenesis.
- Marie-Laure Fogeron
- , Hannah Müller
- & Bodo M.H. Lange
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Interactions between Twist and other core epithelial–mesenchymal transition factors are controlled by GSK3-mediated phosphorylation
Twist is an epithelial–mesenchymal transition regulatory factor that is implicated in neural crest development and cancer. Lander and colleagues show that Twist interacts with Snail proteins to inhibit their function, and that this interaction is regulated by phosphorylation of the Twist C terminus.
- Rachel Lander
- , Talia Nasr
- & Carole LaBonne
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Translation of HTT mRNA with expanded CAG repeats is regulated by the MID1–PP2A protein complex
Expansion of CAG repeats in messenger RNAs is a common feature of various neurodegenerative disorders, including Huntington’s disease. Krauß et al.show that messenger RNAs with expanded CAG repeats bind to a protein complex that regulates translation and promotes overproduction of such aberrant proteins.
- Sybille Krauß
- , Nadine Griesche
- & Susann Schweiger
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| Open AccessPI(4,5)P2 5-phosphatase A regulates PI3K/Akt signalling and has a tumour suppressive role in human melanoma
Inositol polyphosphate 5-phosphatases, such as PIB5PA, terminate signalling downstream of phosophoinositide-3 kinase; however, their biological roles remain unclear. Here the authors report that PIB5PA has a tumour suppressive role in melanoma.
- Yan Ye
- , Lei Jin
- & Xu Dong Zhang
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| Open AccessReal-time single-molecule co-immunoprecipitation analyses reveal cancer-specific Ras signalling dynamics
Co-immunoprecipitation provides static and qualitative information about protein–protein interactions. Lee et al.create real-time movies of single protein–protein interactions during co-immunoprecipitation, and use them to assess the dynamics of mutant Ras proteins derived from tumours.
- Hong-Won Lee
- , Taeyoon Kyung
- & Tae-Young Yoon
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Arabidopsis ubiquitin ligase MIEL1 mediates degradation of the transcription factor MYB30 weakening plant defence
In plants, the regulatory mechanisms that control disease resistance responses remain poorly understood. Marino et al. show that the Arabidopsis E3 ubiquitin ligase MIEL1 interacts with and ubiquitinates the MYB transcription factor (TF), MYB30, leading to proteasomal degradation of MYB30 and attenuation of plant defence.
- Daniel Marino
- , Solène Froidure
- & Susana Rivas
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Extracellular matrix inhibits structural and functional plasticity of dendritic spines in the adult visual cortex
Neuronal connectivity in the mature brain is stabilized by the extracellular matrix. This study shows that degradation of chondroitin sulfate proteoglycans in the matrix increases connectivity in the adult cortex by causing a large increase in motility and functional plasticity of dendritic spines.
- L. de Vivo
- , S. Landi
- & G.M. Ratto
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Cytotoxicity of botulinum neurotoxins reveals a direct role of syntaxin 1 and SNAP-25 in neuron survival
Botulinum toxins can cause substantial neurodegeneration. Peng et al. study cultured rat hippocampal neurons and find that botulinum toxin-induced cytotoxicity occurs only when there is effective cleavage of the SNARE proteins, syntaxin 1 or SNAP-25, by type C and type E botulinum toxins.
- Lisheng Peng
- , Huisheng Liu
- & Min Dong
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Synaptobrevin2 is the v-SNARE required for cytotoxic T-lymphocyte lytic granule fusion
Cytotoxic T lymphocytes kill target cells through the fusion of lytic granules at the immunological synapse. Using high-resolution microscopy techniques Matti et al.identify synaptobrevin2 as the vesicular SNARE protein required for this fusion reaction.
- Ulf Matti
- , Varsha Pattu
- & Jens Rettig
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| Open AccessPeptide hormone ghrelin enhances neuronal excitability by inhibition of Kv7/KCNQ channels
The gut-derived orexigenic hormone, ghrelin, enhances neuronal firing in the substantia nigra pars compacta. This study shows that ghrelin enhances firing of nigral dopaminergic neurons by a novel mechanism in which activation of the PLC/PKC pathway inhibits Kv7 channels.
- Limin Shi
- , Xiling Bian
- & Junxia Xie
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Ephrin-A5/EphA4 signalling controls specific afferent targeting to cochlear hair cells
Cochlear inner and outer hair cells receive afferent innervation from type I and type II spiral ganglion neurons, respectively. Defourny et al. find that, in the absence of ephrin-A5 and its receptor EphA4, a subset of type I spiral ganglion neuron projections invade the outer hair cell area.
- Jean Defourny
- , Anne-Lise Poirrier
- & Brigitte Malgrange
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| Open AccessInterplay between myosin IIA-mediated contractility and actin network integrity orchestrates podosome composition and oscillations
Dendritic cells use protrusive structures called podosomes to probe the extracellular environment. Here the authors reveal how interplay between actin-mediated core growth and myosin-mediated tension regulates podosome protrusion.
- K. van den Dries
- , M.B.M Meddens
- & A. Cambi
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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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FBH1 co-operates with MUS81 in inducing DNA double-strand breaks and cell death following replication stress
DNA replication stress promotes genome instability and cell death. Here Fugger et al.describe how FBH1, via its helicase activity, is required to eliminate cells with excessive DNA replication stress, through the generation of MUS81-induced DNA double-strand breaks.
- Kasper Fugger
- , Wai Kit Chu
- & Claus Storgaard Sørensen
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Selective escape of proteins from the mitochondria during mitophagy
Damaged mitochondria are eliminated from the cell by a form of autophagy called mitophagy. Here the authors show that during mitophagy, specific proteins are rescued from degradation by evacuation from the mitochondria to the endoplasmic reticulum.
- Shotaro Saita
- , Michiko Shirane
- & Keiichi I. Nakayama
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| Open AccessSpatial association with PTEX complexes defines regions for effector export into Plasmodium falciparum-infected erythrocytes
During red blood cell infection, malaria parasites export hundreds of proteins that remodel the host cell surface. Cowman and colleagues identify a putative protein translocator complex spatially associated with exported proteins, revealing the cellular domains involved in protein export.
- David T. Riglar
- , Kelly L. Rogers
- & Alan F. Cowman
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The phosphatase Dullard negatively regulates BMP signalling and is essential for nephron maintenance after birth
Kidney maintenance and function are essential for a healthy organism. Here Nishinakamura and colleagues show that the phosphatase Dullard suppresses BMP signalling and apoptosis in the mouse kidney and that Dullard is required for the maintenance of functional nephrons after birth.
- Masaji Sakaguchi
- , Sazia Sharmin
- & Ryuichi Nishinakamura
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| Open AccessA point mutation in Semaphorin 4A associates with defective endosomal sorting and causes retinal degeneration
Semaphorin 4A is implicated in photoreceptor survival. Nojima and colleagues generate transgenic mice with different mutations in the Sema4A gene and find that point mutation of F350 causes severe degeneration in photoreceptor cells, which can be rescued by virus-mediated gene therapy.
- Satoshi Nojima
- , Toshihiko Toyofuku
- & Atsushi Kumanogoh
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Src activation by β-adrenoreceptors is a key switch for tumour metastasis
The neurotransmitter noradrenaline can regulate cellular processes that contribute to cancer progression, but the underlying mechanisms remain largely unknown. Here the authors identify Src as a key mediator of noradrenaline signalling networks in tumour metastasis.
- Guillermo N. Armaiz-Pena
- , Julie K. Allen
- & Anil K. Sood
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Non-uniform membrane diffusion enables steady-state cell polarization via vesicular trafficking
The mechanism by which proteins become polarized to a specific cortical site in budding yeast cells has been a topic of recent debate. Slaughter et al.show that differing diffusion rates of Cdc42 within plasma membrane environments sustain the polarized state.
- Brian D. Slaughter
- , Jay R. Unruh
- & Rong Li
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MicroRNA-30c inhibits human breast tumour chemotherapy resistance by regulating TWF1 and IL-11
The role of microRNAs in chemotherapy resistance remains to be elucidated. Bockhorn et al.report that microRNA-30c, a human breast tumour prognostic marker, has a key role by targeting the epithelial-to-mesenchymal transition promoter twinfilin 1 and downstream interleukin-11 expression.
- Jessica Bockhorn
- , Rachel Dalton
- & Huiping Liu
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| Open AccessSignalling properties of inorganic polyphosphate in the mammalian brain
Inorganic polyphosphates have been identified in the central nervous system. Holmström and colleagues examine neuroglial cultures in vitro and cardiorespiratory responses in vivo, and find that inorganic polyphosphates trigger calcium-dependent activation of astrocytes and increase cardiorespiratory activity.
- Kira M. Holmström
- , Nephtali Marina
- & Andrey Y. Abramov
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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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Interaction between p68 RNA helicase and Ca2+-calmodulin promotes cell migration and metastasis
Cell migration requires motor protein-driven delivery of proteins to the leading edge. This study shows that p68 RNA helicase behaves as a microtubule-based motor upon binding calmodulin, and that blocking this interaction inhibits cancer cell metastasis.
- Haizhen Wang
- , Xueliang Gao
- & Zhi-Ren Liu
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| Open AccessRab9 and retromer regulate retrograde trafficking of luminal protein required for epithelial tube length control
The development of biological tubes is regulated by mutual interactions between cells and luminal extracellular matrix. Donget al. show that retrograde recycling of luminal chitin deacetylase regulates Drosophila tracheal tubule geometry by restricting length independently of diameter.
- Bo Dong
- , Ken Kakihara
- & Shigeo Hayashi
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| Open AccessThe bipolar assembly domain of the mitotic motor kinesin-5
During mitosis, kinesin-5 motors are thought to crosslink microtubules in a muscle-like sliding filament mechanism. By combining electron microscopy with other structural tools, the authors reveal how four kinesin-5 polypeptides are organized into bipolar minifilaments.
- Seyda Acar
- , David B. Carlson
- & Jonathan M. Scholey
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Splicing factor SRSF3 is crucial for hepatocyte differentiation and metabolic function
Splicing factors, such as the protein SRSF3, regulate mRNA metabolism but are hard to study in vivobecause genetic kockouts are usually lethal. Here, Sen and colleagues create mice with a hepatocyte-specific knockout of Srsf3 and demonstrate its role in hepatocyte differentiation and liver function.
- Supriya Sen
- , Hassan Jumaa
- & Nicholas J. G. Webster
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Activity of the mitochondrial calcium uniporter varies greatly between tissues
The flow of calcium into the mitochondrial matrix is mediated by the mitochondrial calcium uniporter. Fieniet al. apply patch-clamp techniques to mitoplasts isolated from different mouse and Drosophilatissues and find that the mitochondrial calcium uniporter activity varies depending on the tissue studied.
- Francesca Fieni
- , Sung Bae Lee
- & Yuriy Kirichok
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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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Phospho-dependent ubiquitination and degradation of PAR-1 regulates synaptic morphology and tau-mediated Aβ toxicity in Drosophila
PAR-1 inDrosophilahas been identified as a key physiological tau kinase. Lee and colleagues perform genetic screens for regulators of PAR-1 and find that it is targeted for ubiquitination and degradation by the ubiquitin ligase complex SCF(Slimb), and that this pathway modulates synaptic morphology.
- Seongsoo Lee
- , Ji-Wu Wang
- & Bingwei Lu
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PPARγ is an E3 ligase that induces the degradation of NFκB/p65
NFκB/p65 and PPARγ are both transcription factors that perform distinct but overlapping roles in cellular regulation. Hou et al. report that PPARγ acts as an E3 ubiquitin ligase and promotes Lys48-linked ubiquitination and degradation of p65, terminating NFκB-mediated inflammation and tumorigenesis.
- Yongzhong Hou
- , France Moreau
- & Kris Chadee
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| Open AccessTransmembrane insertion of twin-arginine signal peptides is driven by TatC and regulated by TatB
TatA, B and C act together to translocate folded proteins across bacterial and chloroplast membranes, however the precise mechanism remains unclear. Fröbel and colleagues discover that TatC has unforeseen membrane insertase activity, while TatB prevents premature cleavage before translocation.
- Julia Fröbel
- , Patrick Rose
- & Matthias Müller
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The developmental basis of bat wing muscle
Phylogenetic bat studies suggest that powered flight is evolutionarily conserved. Tokita et al.find that bat wing muscles are derived from multiple myogenic sources with different embryonic origins, and that spatiotemporal correlations exist between outgrowth of wing membranes and expansion of wing muscles.
- Masayoshi Tokita
- , Takaaki Abe
- & Kazuo Suzuki
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A role for calpain-dependent cleavage of TDP-43 in amyotrophic lateral sclerosis pathology
The mislocalization and downregulation of the proteins TDP-43 and ADAR2, respectively, are implicated in amyotrophic lateral sclerosis pathology. Yamashita et al. find that downregulation of ADAR2 results in calcium-permeable AMPA receptor-mediated calpain activation and subsequent aberrant cleavage of TDP-43.
- Takenari Yamashita
- , Takuto Hideyama
- & Shin Kwak
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DJ-1 promotes angiogenesis and osteogenesis by activating FGF receptor-1 signaling
Osteoblasts and endothelial cells have important roles in bone regeneration. Kim and colleagues identify the protein DJ-1 as an angiogenic and osteogenic signalling molecule involved in the cross-talk between these cells and show that DJ-1 promotes bone regeneration and fracture healing in mice.
- Jung-Min Kim
- , Hong-In Shin
- & Pann-Ghill Suh
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ASK3 responds to osmotic stress and regulates blood pressure by suppressing WNK1-SPAK/OSR1 signaling in the kidney
Cells must be able to sense and respond to changes in osmotic pressure, which can be lethal. Here, Naguro and colleagues reveal a role for the protein kinase ASK3 in sensing osmotic stress in the mouse kidney and show that ASK3 contributes to the regulation of blood pressure.
- Isao Naguro
- , Tsuyoshi Umeda
- & Hidenori Ichijo
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Preotic neural crest cells contribute to coronary artery smooth muscle involving endothelin signalling
Endothelin-1 regulates cardiovascular development by acting on neural crest cells. Here endothelin-1-deficient mice are studied, revealing that preotic neural crest cells differentiate into coronary artery smooth muscle cells through endothelin-1-dependent mechanisms.
- Yuichiro Arima
- , Sachiko Miyagawa-Tomita
- & Hiroki Kurihara
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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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Receptor tyrosine kinase ErbB2 translocates into mitochondria and regulates cellular metabolism
ErbB2 is a receptor tyrosine kinase that localizes to the plasma membrane. Dinget al. now show that ErbB2 also localizes to mitochondria, where it regulates mitochondrial respiratory function and resistance to cancer chemotherapy.
- Yan Ding
- , Zixing Liu
- & Ming Tan
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Cooperation between different RNA virus genomes produces a new phenotype
RNA viruses are known to rapidly evolve new features through errors in replication and reshuffling of genomic segments. These authors report another strategy used by the measles virus to improve infectivity; the cooperation between wild-type and mutant fusion proteins in the same viral particle.
- Yuta Shirogane
- , Shumpei Watanabe
- & Yusuke Yanagi
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Molecular determinants of selective clearance of protein inclusions by autophagy
Dysfunctional or aggregated proteins in cells are degraded by autophagy. Wong et al.study aggregates of the protein synphilin-1 and show that ubiquitination alters their dynamic properties, which determines whether the aggregates are degraded via basal or inducible forms of autophagy.
- Esther Wong
- , Eloy Bejarano
- & Ana Maria Cuervo
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The RB family is required for the self-renewal and survival of human embryonic stem cells
While human embryonic stem cells (ESC) hold great therapeutic promise, many aspects of their basic biology remain poorly understood. Conklin et al.show that too much or too little activation of RB family proteins is detrimental to human ESC populations and identify unique cell cycle regulatory networks in these cells.
- Jamie F. Conklin
- , Julie Baker
- & Julien Sage
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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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| 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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| Open AccessLaminin E8 fragments support efficient adhesion and expansion of dissociated human pluripotent stem cells
The use of animal products as culture substrates for human embryonic stem cell and induced pluripotent stem cell culture raises numerous safety concerns in a therapeutic setting. Miyazaki et al.. show that minimal fragments of human laminins provide a more effective support for the culture of these cell types.
- Takamichi Miyazaki
- , Sugiko Futaki
- & Eihachiro Kawase
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Involvement of PGC-1α in the formation and maintenance of neuronal dendritic spines
PGC-1α regulates mitochondrial biogenesis and adaptive thermogenesis. Cheng and colleagues alter the expression of PGC-1α in primary neuronal cultures and in the adult mouse brain, and find that it regulates dendritic spine formation and maintenance by mediating the synaptogenic actions of BDNF and CREB.
- Aiwu Cheng
- , Ruiqian Wan
- & Mark P. Mattson
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| Open AccessPhosphorylation of VE-cadherin is modulated by haemodynamic forces and contributes to the regulation of vascular permeability in vivo
Vascular endothelial-cadherin is a junctional protein implicated in the control of vascular permeability. Orsenigo et al.find that vascular endothelial-cadherin is phosphorylated in veins but not in arteries of mice, and that this sensitizes vessels to rapid changes in permeability in response to inflammatory mediators.
- Fabrizio Orsenigo
- , Costanza Giampietro
- & Elisabetta Dejana
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| Open AccessThe Hedgehog signalling pathway regulates autophagy
Autophagy is a cellular process that controls protein and organelle turnover. Jimenez-Sanchez and colleagues demonstrate in cultured mammalian cells and in fruit fly larvae that autophagy is regulated by Hedgehoc signalling, a pathway that is important for early embryonic development.
- Maria Jimenez-Sanchez
- , Fiona M. Menzies
- & David C. Rubinsztein
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A monomeric red fluorescent protein with low cytotoxicity
Fluorescent proteins are widely used to image cellular structures. Here, Shemiakina and colleagues develop an enhanced version of a red fluorescent protein that is monomeric and less cytotoxic, thereby improving the quality of images that can be obtained in the red part of the visible spectrum.
- I.I. Shemiakina
- , G.V. Ermakova
- & D. Shcherbo
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