4,980 results match your criteria mutant hypersensitive

Functional overlap of two major facilitator superfamily transporter, ZIF1, and ZIFL1 in zinc and iron homeostasis.

Biochem Biophys Res Commun 2021 May 5;560:7-13. Epub 2021 May 5.

Department of Biological Sciences, Dartmouth College, Hanover, NH, 03755, USA.

Zinc and iron are essential micronutrients for plant growth, and their homeostasis must be tightly regulated. Previously, it has been shown that Zinc-Induced Facilitator 1 (ZIF1) is involved in basal Zn tolerance by controlling the vacuolar storage of nicotianamine (NA). However, knowledge of the functional roles of two ZIF1 paralogs, ZIF-LIKE1 (ZIFL1) and ZIFL2, in metal homeostasis remains limited. Read More

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Exploiting vulnerabilities of SWI/SNF chromatin remodelling complexes for cancer therapy.

Oncogene 2021 May 3. Epub 2021 May 3.

Institute of Pharmaceutical Chemistry, Goethe University Frankfurt, Frankfurt am Main, Germany.

Multi-subunit ATPase-dependent chromatin remodelling complexes SWI/SNF (switch/sucrose non-fermentable) are fundamental epigenetic regulators of gene transcription. Functional genomic studies revealed a remarkable mutation prevalence of SWI/SNF-encoding genes in 20-25% of all human cancers, frequently driving oncogenic programmes. Some SWI/SNF-mutant cancers are hypersensitive to perturbations in other SWI/SNF subunits, regulatory proteins and distinct biological pathways, often resulting in sustained anticancer effects and synthetic lethal interactions. Read More

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Functional consequences of a rare missense BARD1 c.403G>A germline mutation identified in a triple-negative breast cancer patient.

Breast Cancer Res 2021 May 1;23(1):53. Epub 2021 May 1.

State Key Laboratory of Genetic Engineering, School of Life Sciences and Shanghai Cancer Center, Fudan University, Shanghai, China.

We identified a rare missense germline mutation in BARD1 (c.403G>A or p.Asp135Asn) as pathogenic using integrated genomics and transcriptomics profiling of germline and tumor samples from an early-onset triple-negative breast cancer patient who later was administrated with a PARP inhibitor for 2 months. Read More

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Global Analysis of RNA-Dependent RNA Polymerase-Dependent Small RNAs Reveals New Substrates and Functions for These Proteins and SGS3 in Arabidopsis.

Noncoding RNA 2021 Apr 27;7(2). Epub 2021 Apr 27.

Department of Biology, University of Pennsylvania, Philadelphia, PA 19104, USA.

RNA silencing pathways control eukaryotic gene expression transcriptionally or posttranscriptionally in a sequence-specific manner. In RNA silencing, the production of double-stranded RNA (dsRNA) gives rise to various classes of 20-24 nucleotide (nt) small RNAs (smRNAs). In , smRNAs are often derived from long dsRNA molecules synthesized by one of the six genomically encoded RNA-dependent RNA Polymerase (RDR) proteins. Read More

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A Genome-Wide Screen in Reveals a Critical Role for Oxidative Phosphorylation in Cellular Tolerance to Lithium Hexafluorophosphate.

Cells 2021 Apr 13;10(4). Epub 2021 Apr 13.

State Key Laboratory of Subtropical Silviculture, School of Forestry and Biotechnology, Zhejiang A&F University, Lin'an, Hangzhou 311300, China.

Lithium hexafluorophosphate (LiPF) is one of the leading electrolytes in lithium-ion batteries, and its usage has increased tremendously in the past few years. Little is known, however, about its potential environmental and biological impacts. In order to improve our understanding of the cytotoxicity of LiPF and the specific cellular response mechanisms to it, we performed a genome-wide screen using a yeast () deletion mutant collection and identified 75 gene deletion mutants that showed LiPF sensitivity. Read More

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Mitochondrial Function and Anesthetic Sensitivity in the Mouse Spinal Cord.

Anesthesiology 2021 Apr 28. Epub 2021 Apr 28.

Background: Ndufs4 knockout (KO) mice are defective in mitochondrial complex I function and hypersensitive to inhibition of spinal cord-mediated response to noxious stimuli by volatile anesthetics. It was hypothesized that, compared to wild-type, synaptic or intrinsic neuronal function is hypersensitive to isoflurane in spinal cord slices from knockout mice.

Methods: Neurons from slices of the vestibular nucleus, central medial thalamus, and spinal cord from wild-type and the global Ndufs4 knockout were patch clamped. Read More

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HEXOKINASE1 signalling promotes shoot branching and interacts with cytokinin and strigolactone pathways.

New Phytol 2021 Apr 28. Epub 2021 Apr 28.

School of Biological Sciences, The University of Queensland, St. Lucia, QLD, 4072, Australia.

Plant architecture is controlled by several endogenous signals including hormones and sugars. However, only little is known about the nature and roles of the sugar signalling pathways in this process. Here we test whether the sugar signalling pathway mediated by HEXOKINASE1 (HXK1) is involved in the control of shoot branching. Read More

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SPLICING FACTOR1 Is Important in Chloroplast Development under Cold Stress.

Plant Physiol 2020 Oct;184(2):973-987

Shanghai Key Laboratory of Plant Molecular Sciences, College of Life Sciences, Shanghai Normal University, Shanghai 200234, China.

RNA SPLICING FACTOR1 (SF1) is responsible for recognizing the branch point site (BPS) sequence in introns and is critical for pre-mRNA splicing. In Arabidopsis (Arabidopsis thaliana), splicing factor1 (AtSF1) has been shown to retain the conserved function, but it is unexpected that null atsf1 mutants are viable. Here, we identified an allele of atsf1, named suppressor of thf1-4 (sot4), from suppressor screening for leaf variegation of thylakoid formation1. Read More

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October 2020

PI4Kγ2 Interacts with E3 Ligase MIEL1 to Regulate Auxin Metabolism and Root Development.

Plant Physiol 2020 Oct;184(2):933-944

School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai 200240, China.

Root development is important for normal plant growth and nutrient absorption. Studies have revealed the involvement of various factors in this complex process, improving our understanding of the relevant regulatory mechanisms. Here, we functionally characterize the role of Arabidopsis (Arabidopsis thaliana) phosphatidylinositol 4-kinase γ2 (PI4Kγ2) in root elongation regulation, which functions to modulate stability of the RING-type E3 ligase MYB30-INTERACTING E3 LIGASE1 (MIEL1) and auxin metabolism. Read More

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October 2020

Role of Protein Phosphatase1 Regulatory Subunit3 in Mediating the Abscisic Acid Response.

Plant Physiol 2020 Nov;184(3):1317-1332

Ministry of Education Key Laboratory of Cell Activities and Stress Adaptations, School of Life Sciences, Lanzhou University, Lanzhou 730000, China.

Protein phosphatase1 (PP1) plays important roles in eukaryotes, including in plant hormone responses, and functions as a holoenzyme that consists of catalytic and regulatory subunits. Animal genomes encode ∼200 PP1-interacting proteins; by contrast, only a few have been reported in plants. In this study, PP1 Regulatory Subunit3 (PP1R3), a protein that interacts with PP1 in Arabidopsis (Arabidopsis thaliana), was characterized by mass spectrometry. Read More

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November 2020

Structural variation at the maize WUSCHEL1 locus alters stem cell organization in inflorescences.

Nat Commun 2021 04 22;12(1):2378. Epub 2021 Apr 22.

Waksman Institute of Microbiology, Rutgers University, Piscataway, NJ, 08854-8020, USA.

Structural variation in plant genomes is a significant driver of phenotypic variability in traits important for the domestication and productivity of crop species. Among these are traits that depend on functional meristems, populations of stem cells maintained by the CLAVATA-WUSCHEL (CLV-WUS) negative feedback-loop that controls the expression of the WUS homeobox transcription factor. WUS function and impact on maize development and yield remain largely unexplored. Read More

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Regulation of Lateral Root Development by Shoot-Sensed Far-Red Light via HY5 Is Nitrate-Dependent and Involves the NRT2.1 Nitrate Transporter.

Front Plant Sci 2021 31;12:660870. Epub 2021 Mar 31.

Plant Ecophysiology, Department of Biology, Faculty of Science, Utrecht University, Utrecht, Netherlands.

Plants are very effective in responding to environmental changes during competition for light and nutrients. Low Red:Far-Red (low R:FR)-mediated neighbor detection allows plants to compete successfully with other plants for available light. This above-ground signal can also reduce lateral root growth by inhibiting lateral root emergence, a process that might help the plant invest resources in shoot growth. Read More

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Mirogabalin activates the descending noradrenergic system by binding to the αδ-1 subunit of voltage-gated Ca channels to generate analgesic effects.

J Pharmacol Sci 2021 May 7;146(1):33-39. Epub 2021 Jan 7.

Laboratory of Pharmacology, School of Pharmaceutical Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan; Medicinal Research Laboratories, School of Pharmacy, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan. Electronic address:

Gabapentinoids such as gabapentin and pregabalin, which bind specifically to the αδ subunit of voltage-gated Ca channels, are used for first-line treatment of neuropathic pain. Here, we examined the analgesic effect of mirogabalin besilate (referred to simply as mirogabalin), a novel gabapentinoid, focusing on its action on the spinal cord and the descending noradrenergic pain inhibitory system. When administered systemically (10 and 30 mg/kg, intraperitoneally (i. Read More

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N -Methyladenosine mRNA methylation is important for salt stress tolerance in Arabidopsis.

Plant J 2021 Apr 12. Epub 2021 Apr 12.

Jiangsu Key Laboratory of Phylogenomics and Comparative Genomics, School of Life Sciences, Jiangsu Normal University, Xuzhou, Jiangsu Province, 221116, China.

As the most abundant internal modification of mRNA, N -methyladenosine (m A) methylation of RNA is emerging as a new layer of epitranscriptomic gene regulation in cellular processes, including embryo development, flowering-time control, microspore generation and fruit ripening, in plants. However, the cellular role of m A in plant responses to environmental stimuli remains largely unexplored. In this study, we show that m A methylation plays an important role in salt stress tolerance in Arabidopsis. Read More

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The Genome-Wide EMS Mutagenesis Bias Correlates With Sequence Context and Chromatin Structure in Rice.

Front Plant Sci 2021 24;12:579675. Epub 2021 Mar 24.

Guangdong Provincial Key Laboratory of Biotechnology for Plant Development, School of Life Sciences, South China Normal University, Guangzhou, China.

Ethyl methanesulfonate (EMS) is a chemical mutagen believed to mainly induce G/C to A/T transitions randomly in plant genomes. However, mutant screening for phenotypes often gets multiple alleles for one gene but no mutant for other genes. We investigated the potential EMS mutagenesis bias and the possible correlations with sequence context and chromatin structure using the whole genome resequencing data collected from 52 rice EMS mutants. Read More

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TMK4 receptor kinase negatively modulates ABA signaling by phosphorylating ABI2 and enhancing its activity.

J Integr Plant Biol 2021 Apr 3. Epub 2021 Apr 3.

College of Biology, State Key Laboratory of Chemo/Biosensing and Chemometrics and Hunan Key Laboratory of Plant Functional Genomics and Developmental Regulation Hunan University, Changsha, 410082, P. R. China.

In plants, clade A type 2C protein phosphatases (PP2CAs) have emerged as major players in abscisic acid (ABA)-regulated stress responses by inhibiting protein kinase activity. However, how different internal and external environmental signals modulate the activity of PP2CAs are not well known. The Transmembrane Kinase (TMK) protein 4 (TMK4), one member of a previously identified receptor kinase subfamily on the plasma membrane that play vital roles in plant cell growth, directly interacts with PP2CAs member (ABA-Insensitive 2, ABI2). Read More

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Insights into the Role of Transcriptional Gene Silencing in Response to Herbicide-Treatments in .

Int J Mol Sci 2021 Mar 24;22(7). Epub 2021 Mar 24.

Department of Crop Science, Federal University of Rio Grande do Sul, Porto Alegre, RS 91540-000, Brazil.

Herbicide resistance is broadly recognized as the adaptive evolution of weed populations to the intense selection pressure imposed by the herbicide applications. Here, we tested whether transcriptional gene silencing (TGS) and RNA-directed DNA Methylation (RdDM) pathways modulate resistance to commonly applied herbicides. Using wild-type plants exposed to sublethal doses of glyphosate, imazethapyr, and 2,4-D, we found a partial loss of TGS and increased susceptibility to herbicides in six out of 11 tested TGS/RdDM mutants. Read More

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The E3 Ubiquitin Ligase BRIZ Functions in Abscisic Acid Response.

Front Plant Sci 2021 16;12:641849. Epub 2021 Mar 16.

Department of Molecular and Cellular Biology, University of California, Davis, Davis, CA, United States.

The ubiquitin system is essential for multiple hormone signaling pathways in plants. Here, we show that the E3 ligase BRIZ, a heteromeric ligase that consists minimally of BRIZ1 and BRIZ2 proteins, functions in abscisic acid (ABA) signaling or response. and homozygous mutants either fail to germinate or emerge later than wild-type seedlings, with little cotyledon expansion or root elongation and no visible greening. Read More

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The nucleolar protein SAHY1 is involved in pre-rRNA processing and normal plant growth.

Plant Physiol 2021 Apr;185(3):1039-1058

Institute of Plant and Microbial Biology, Academia Sinica, Taipei, Taiwan.

Although the nucleolus is involved in ribosome biogenesis, the functions of numerous nucleolus-localized proteins remain unclear. In this study, we genetically isolated Arabidopsis thaliana salt hypersensitive mutant 1 (sahy1), which exhibits slow growth, short roots, pointed leaves, and sterility. SAHY1 encodes an uncharacterized protein that is predominantly expressed in root tips, early developing seeds, and mature pollen grains and is mainly restricted to the nucleolus. Read More

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The BAX-binding protein MOAP1 associates with LC3 and promotes closure of the phagophore.

Autophagy 2021 Mar 30:1-15. Epub 2021 Mar 30.

Department of Pharmacy, Faculty of Science, National University of Singapore, Singapore, Singapore.

MOAP1 (modulator of apoptosis 1) is a BAX-binding protein tightly regulated by the ubiquitin-proteasome system. Apoptotic stimuli stabilize MOAP1 protein and facilitate its interaction with BAX to promote apoptosis. Here we show that in contrast to being resistant to apoptotic stimuli, MOAP1-deficient cells are hypersensitive to cell death mediated by starvation rendered by EBSS treatment. Read More

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Characterization of a TNFR2-Selective Agonistic TNF-α Mutant and Its Derivatives as an Optimal Regulatory T Cell Expander.

J Immunol 2021 Apr 29;206(8):1740-1751. Epub 2021 Mar 29.

Laboratory of Cellular and Molecular Physiology, The Faculty of Pharmaceutical Sciences, Kobe Gakuin University, Chuo-ku, Kobe 650-8586, Japan;

Regulatory T cells (Tregs) are a subpopulation of lymphocytes that play a role in suppressing and regulating immune responses. Recently, it was suggested that controlling the functions and activities of Tregs might be applicable to the treatment of human diseases such as autoimmune diseases, organ transplant rejection, and graft-versus-host disease. TNF receptor type 2 (TNFR2) is a target molecule that modulates Treg functions. Read More

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A plant-unique ESCRT component, FYVE4, regulates multivesicular endosome biogenesis and plant growth.

New Phytol 2021 Mar 27. Epub 2021 Mar 27.

Guangdong Provincial Key Laboratory of Biotechnology for Plant Development, School of Life Sciences, South China Normal University, Guangzhou, 510631, China.

During evolution, land plants generated unique proteins that participate in endosomal sorting and multivesicular endosome (MVE) biogenesis, many of them with specific phosphoinositide-binding capabilities. Nonetheless, the function of most plant phosphoinositide-binding proteins in endosomal trafficking remains elusive. Here, we analysed several Arabidopsis mutants lacking predicted phosphoinositide-binding proteins and first identified fyve4-1 as a mutant with a hypersensitive response to high-boron conditions and defects in degradative vacuolar sorting of membrane proteins such as the borate exporter BOR1-GFP. Read More

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Protein farnesylation negatively regulates brassinosteroid signaling via reducing BES1 stability in Arabidopsis thaliana.

J Integr Plant Biol 2021 Mar 25. Epub 2021 Mar 25.

Ministry of Education Key Laboratory of Cell Activities and Stress Adaptations, School of Life Sciences, Lanzhou University, Lanzhou, 730000, China.

Brassinosteroids (BRs) are a group of steroidal phytohormones, playing critical roles in almost all physiological aspects during the life span of a plant. In Arabidopsis, BRs are perceived at the cell surface, triggering a reversible phosphorylation-based signaling cascade that leads to the activation and nuclear accumulation of a family of transcription factors, represented by BES1 and BZR1. Protein farnesylation is a type of post-translational modification, functioning in many important cellular processes. Read More

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Contributions of lipopolysaccharide and the type IVB secretion system to Coxiella burnetii vaccine efficacy and reactogenicity.

NPJ Vaccines 2021 Mar 19;6(1):38. Epub 2021 Mar 19.

Coxiella Pathogenesis Section, Laboratory of Bacteriology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA.

Coxiella burnetii is the bacterial causative agent of the zoonosis Q fever. The current human Q fever vaccine, Q-VAX, is a fixed, whole cell vaccine (WCV) licensed solely for use in Australia. C. Read More

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Reduction of OsMPK6 activity by a R89K mutation induces cell death and bacterial blight resistance in rice.

Plant Cell Rep 2021 May 17;40(5):835-850. Epub 2021 Mar 17.

State Key Laboratory of Rice Biology and China National Center for Rice Improvement, China National Rice Research Institute, Hangzhou, 311401, China.

Key Message: The R89 is essential for the kinase activity of OsMPK6 which negatively regulates cell death and defense response in rice. Mitogen-activated protein kinase cascade plays critical roles in various vital activities, including the plant immune response, but the mechanisms remain elusive. Here, we identified and characterized a rice lesion mimic mutant osmpk6 which displayed hypersensitive response-like lesions in company with cell death and hydrogen peroxide hyperaccumulation. Read More

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Challenges and Opportunities for Drug Repositioning in Fibrodysplasia Ossificans Progressiva.

Biomedicines 2021 Feb 19;9(2). Epub 2021 Feb 19.

Department of Cell and Chemical Biology, Cardiovascular Cell Biology, Leiden University Medical Center, Einthovenweg 20, 2333 ZC Leiden, The Netherlands.

Fibrodysplasia ossificans progressiva (FOP) is an ultrarare congenital disease that progresses through intermittent episodes of bone formation at ectopic sites. FOP patients carry heterozygous gene point mutations in activin A receptor type I , encoding the bone morphogenetic protein (BMP) type I serine/threonine kinase receptor ALK2, termed activin receptor-like kinase (ALK)2. The mutant ALK2 displays neofunctional responses to activin, a closely related BMP cytokine that normally inhibits regular bone formation. Read More

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February 2021

A small molecule inhibits cell elongation by modulating cell wall polysaccharide composition in .

Cell Surf 2021 Dec 2;7:100049. Epub 2021 Feb 2.

National Key Laboratory of Plant Molecular Genetics, CAS Center for Excellence in Molecular Plant Sciences, Shanghai Institute of Plant Physiology and Ecology, Chinese Academy of Sciences, Shanghai 200032, China.

The plant primary cell wall is comprised of pectin, cellulose and hemicelluloses, whose dynamic interactions play essential roles in plant cell elongation. Through a chemical genetics screening, we identified a small molecule, named cell wall modulator (CWM), which disrupted cell growth and deformed cell shape in etiolated hypocotyl. A pectin defective mutant , identified from screening an EMS mutant library, showed a reduced sensitivity to CWM treatment. Read More

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December 2021

ATF4 selectively regulates heat nociception and contributes to kinesin-mediated TRPM3 trafficking.

Nat Commun 2021 03 3;12(1):1401. Epub 2021 Mar 3.

Medical Research Center of Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, 106 Zhongshan Rd. 2, Guangzhou, China.

Effective treatments for patients suffering from heat hypersensitivity are lacking, mostly due to our limited understanding of the pathogenic mechanisms underlying this disorder. In the nervous system, activating transcription factor 4 (ATF4) is involved in the regulation of synaptic plasticity and memory formation. Here, we show that ATF4 plays an important role in heat nociception. Read More

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Activation of SnRK2 by Raf-like kinase ARK represents a primary mechanism of ABA and abiotic stress responses.

Plant Physiol 2021 Mar;185(2):533-546

Graduate School of Science and Engineering, Saitama University, Shimo-ohkubo 255, Sakura-ku, Saitama 338-8570, Japan.

The Raf-like protein kinase abscisic acid (ABA) and abiotic stress-responsive Raf-like kinase (ARK) previously identified in the moss Physcomitrium (Physcomitrella) patens acts as an upstream regulator of subgroup III SNF1-related protein kinase2 (SnRK2), the key regulator of ABA and abiotic stress responses. However, the mechanisms underlying activation of ARK by ABA and abiotic stress for the regulation of SnRK2, including the role of ABA receptor-associated group A PP2C (PP2C-A), are not understood. We identified Ser1029 as the phosphorylation site in the activation loop of ARK, which provided a possible mechanism for regulation of its activity. Read More

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The Lack of SNARE Protein Homolog Syn8 Influences Biofilm Formation of .

Front Cell Dev Biol 2021 12;9:607188. Epub 2021 Feb 12.

School of Life Sciences and Technology, Tokyo Institute of Technology, Yokohama, Japan.

Biofilm formation of species is considered to be a pathogenic factor of host infection. Since biofilm formation of has not been as well studied as that of , we performed genetic screening of , and three candidate genes associated with biofilm formation were identified. (CAGL0H06325g) was selected as the most induced gene in biofilm cells for further research. Read More

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February 2021