Knocking out barriers to engineered cell activity
Source: ScienceNOW - February 27, 2020 Category: Science Authors: Hamilton, J. R., Doudna, J. A. Tags: Cell Biology, Medicine, Diseases perspective Source Type: news
Angiotensin and biased analogs induce structurally distinct active conformations within a GPCR
Biased agonists of G protein–coupled receptors (GPCRs) preferentially activate a subset of downstream signaling pathways. In this work, we present crystal structures of angiotensin II type 1 receptor (AT1R) (2.7 to 2.9 angstroms) bound to three ligands with divergent bias profiles: the balanced endogenous agonist angiotensin II (AngII) and two strongly β-arrestin–biased analogs. Compared with other ligands, AngII promotes more-substantial rearrangements not only at the bottom of the ligand-binding pocket but also in a key polar network in the receptor core, which forms a sodium-binding site in most GPCRs. ...
Source: ScienceNOW - February 20, 2020 Category: Science Authors: Wingler, L. M., Skiba, M. A., McMahon, C., Staus, D. P., Kleinhenz, A. L. W., Suomivuori, C.-M., Latorraca, N. R., Dror, R. O., Lefkowitz, R. J., Kruse, A. C. Tags: Biochemistry, Cell Biology reports Source Type: news
Molecular mechanism of biased signaling in a prototypical G protein-coupled receptor
Biased signaling, in which different ligands that bind to the same G protein–coupled receptor preferentially trigger distinct signaling pathways, holds great promise for the design of safer and more effective drugs. Its structural mechanism remains unclear, however, hampering efforts to design drugs with desired signaling profiles. Here, we use extensive atomic-level molecular dynamics simulations to determine how arrestin bias and G protein bias arise at the angiotensin II type 1 receptor. The receptor adopts two major signaling conformations, one of which couples almost exclusively to arrestin, whereas the other al...
Source: ScienceNOW - February 20, 2020 Category: Science Authors: Suomivuori, C.-M., Latorraca, N. R., Wingler, L. M., Eismann, S., King, M. C., Kleinhenz, A. L. W., Skiba, M. A., Staus, D. P., Kruse, A. C., Lefkowitz, R. J., Dror, R. O. Tags: Biochemistry, Cell Biology r-articles Source Type: news
The 19th Annual Wiley Prize in Biomedical Sciences awarded for pioneering studies in cell biology
(Wiley) The Wiley Foundation is pleased to announce that the 19th annual Wiley Prize in Biomedical Sciences will be awarded to Clifford Brangwynne, Anthony Hyman, and Michael Rosen. (Source: EurekAlert! - Social and Behavioral Science)
Source: EurekAlert! - Social and Behavioral Science - February 18, 2020 Category: International Medicine & Public Health Source Type: news
Researchers discover a method that can potentially block tumor growth in animal subjects with cancer
(Natural News) In an exciting new development, scientists from the University of Pennsylvania’s Perelman School of Medicine have found what they term the Achilles’ Heel of cancerous tumors. According to a study published in Nature Cell Biology, activating transcription factor 4 (ATF4) could be the key to conquering cancer. While millions of our body’s cells... (Source: NaturalNews.com)
Source: NaturalNews.com - February 13, 2020 Category: Consumer Health News Source Type: news
An AMPK-caspase-6 axis controls liver damage in nonalcoholic steatohepatitis
Liver cell death has an essential role in nonalcoholic steatohepatitis (NASH). The activity of the energy sensor adenosine monophosphate (AMP)–activated protein kinase (AMPK) is repressed in NASH. Liver-specific AMPK knockout aggravated liver damage in mouse NASH models. AMPK phosphorylated proapoptotic caspase-6 protein to inhibit its activation, keeping hepatocyte apoptosis in check. Suppression of AMPK activity relieved this inhibition, rendering caspase-6 activated in human and mouse NASH. AMPK activation or caspase-6 inhibition, even after the onset of NASH, improved liver damage and fibrosis. Once phosphorylati...
Source: ScienceNOW - February 6, 2020 Category: Science Authors: Zhao, P., Sun, X., Chaggan, C., Liao, Z., in Wong, K., He, F., Singh, S., Loomba, R., Karin, M., Witztum, J. L., Saltiel, A. R. Tags: Cell Biology, Medicine, Diseases r-articles Source Type: news
Clinical uses of cellular communication
Source: ScienceNOW - February 6, 2020 Category: Science Authors: Alderton, G. Tags: Cell Biology, Immunology, Medicine, Diseases twis Source Type: news
The biology, function, and biomedical applications of exosomes
The study of extracellular vesicles (EVs) has the potential to identify unknown cellular and molecular mechanisms in intercellular communication and in organ homeostasis and disease. Exosomes, with an average diameter of ~100 nanometers, are a subset of EVs. The biogenesis of exosomes involves their origin in endosomes, and subsequent interactions with other intracellular vesicles and organelles generate the final content of the exosomes. Their diverse constituents include nucleic acids, proteins, lipids, amino acids, and metabolites, which can reflect their cell of origin. In various diseases, exosomes offer a window into...
Source: ScienceNOW - February 6, 2020 Category: Science Authors: Kalluri, R., LeBleu, V. S. Tags: Cell Biology, Immunology, Medicine, Diseases, Online Only review Source Type: news
Parkinson's and the immune system
(Ruhr-University Bochum) Mutations in the Parkin gene are a common cause of hereditary forms of Parkinson's disease. Similar to Parkin, the neighboring Parkin Co-Regulated Gene PACRG regulates a signalling pathway that plays an important role in the innate immune system. This was discovered by a team of researchers led by Professor Konstanze Winklhofer from the Department of Molecular Cell Biology at Ruhr-Universit ä t Bochum (RUB). (Source: EurekAlert! - Medicine and Health)
Source: EurekAlert! - Medicine and Health - February 5, 2020 Category: International Medicine & Public Health Source Type: news
New Director for MRC Laboratory for Molecular Cell Biology at UCL
The MRC is pleased to announce Professor Alison Lloyd as the new Director of the MRC Laboratory for Molecular Cell Biology at UCL. (Source: Medical Research Council General News)
Source: Medical Research Council General News - February 5, 2020 Category: Research Source Type: news
Endoplasmic reticulum contact sites regulate the dynamics of membraneless organelles
Tethered interactions between the endoplasmic reticulum (ER) and other membrane-bound organelles allow for efficient transfer of ions and/or macromolecules and provide a platform for organelle fission. Here, we describe an unconventional interface between membraneless ribonucleoprotein granules, such as processing bodies (P-bodies, or PBs) and stress granules, and the ER membrane. We found that PBs are tethered at molecular distances to the ER in human cells in a tunable fashion. ER-PB contact and PB biogenesis were modulated by altering PB composition, ER shape, or ER translational capacity. Furthermore, ER contact sites ...
Source: ScienceNOW - January 30, 2020 Category: Science Authors: Lee, J. E., Cathey, P. I., Wu, H., Parker, R., Voeltz, G. K. Tags: Cell Biology, Online Only r-articles Source Type: news
Monosomes actively translate synaptic mRNAs in neuronal processes
In this study, we used polysome profiling together with ribosome footprinting of microdissected rodent synaptic regions to reveal a surprisingly high number of dendritic and/or axonal transcripts preferentially associated with monosomes (single ribosomes). Furthermore, the neuronal monosomes were in the process of active protein synthesis. Most mRNAs showed a similar translational status in the cell bodies and neurites, but some transcripts exhibited differential ribosome occupancy in the compartments. Monosome-preferring transcripts often encoded high-abundance synaptic proteins. Thus, monosome translation contributes to ...
Source: ScienceNOW - January 30, 2020 Category: Science Authors: Biever, A., Glock, C., Tushev, G., Ciirdaeva, E., Dalmay, T., Langer, J. D., Schuman, E. M. Tags: Cell Biology, Neuroscience, Online Only r-articles Source Type: news
N6-methyladenosine of chromosome-associated regulatory RNA regulates chromatin state and transcription
N6-methyladenosine (m6A) regulates stability and translation of messenger RNA (mRNA) in various biological processes. In this work, we show that knockout of the m6A writer Mettl3 or the nuclear reader Ythdc1 in mouse embryonic stem cells increases chromatin accessibility and activates transcription in an m6A-dependent manner. We found that METTL3 deposits m6A modifications on chromosome-associated regulatory RNAs (carRNAs), including promoter-associated RNAs, enhancer RNAs, and repeat RNAs. YTHDC1 facilitates the decay of a subset of these m6A-modified RNAs, especially elements of the long interspersed element-1 family, th...
Source: ScienceNOW - January 30, 2020 Category: Science Authors: Liu, J., Dou, X., Chen, C., Chen, C., Liu, C., Xu, M. M., Zhao, S., Shen, B., Gao, Y., Han, D., He, C. Tags: Cell Biology, Molecular Biology reports Source Type: news
Kiss and run: How cells sort and recycle their components
(University of Basel) What can be reused and what can be disposed of? Cells also face this tricky task. Researchers from the Biozentrum of the University of Basel have now discovered a cellular machine, called FERARI, that sorts out usable proteins for recycling. In Nature Cell Biology, they explain how FERARI works and why it is so special. (Source: EurekAlert! - Biology)
Source: EurekAlert! - Biology - January 27, 2020 Category: Biology Source Type: news
Phase separation provides a mechanism to reduce noise in cells
In this study, we used a physical model that links noise in protein concentration to theory of phase separation to show that liquid droplets can effectively reduce noise. We provide experimental support for noise reduction by phase separation using engineered proteins that form liquid-like compartments in mammalian cells. Thus, phase separation can play an important role in biological signal processing and control. (Source: ScienceNOW)
Source: ScienceNOW - January 23, 2020 Category: Science Authors: Klosin, A., Oltsch, F., Harmon, T., Honigmann, A., Jülicher, F., Hyman, A. A., Zechner, C. Tags: Biochemistry, Cell Biology reports Source Type: news
Four glial cells regulate ER stress resistance and longevity via neuropeptide signaling in C. elegans
The ability of the nervous system to sense cellular stress and coordinate protein homeostasis is essential for organismal health. Unfortunately, stress responses that mitigate disturbances in proteostasis, such as the unfolded protein response of the endoplasmic reticulum (UPRER), become defunct with age. In this work, we expressed the constitutively active UPRER transcription factor, XBP-1s, in a subset of astrocyte-like glia, which extended the life span in Caenorhabditis elegans. Glial XBP-1s initiated a robust cell nonautonomous activation of the UPRER in distal cells and rendered animals more resistant to protein aggr...
Source: ScienceNOW - January 23, 2020 Category: Science Authors: Frakes, A. E., Metcalf, M. G., Tronnes, S. U., Bar-Ziv, R., Durieux, J., Gildea, H. K., Kandahari, N., Monshietehadi, S., Dillin, A. Tags: Cell Biology, Neuroscience reports Source Type: news
A two-way molecular dialogue between embryo and endosperm is required for seed development
The plant embryonic cuticle is a hydrophobic barrier deposited de novo by the embryo during seed development. At germination, it protects the seedling from water loss and is, thus, critical for survival. Embryonic cuticle formation is controlled by a signaling pathway involving the ABNORMAL LEAF SHAPE1 subtilase and the two GASSHO receptor-like kinases. We show that a sulfated peptide, TWISTED SEED1 (TWS1), acts as a GASSHO ligand. Cuticle surveillance depends on the action of the subtilase, which, unlike the TWS1 precursor and the GASSHO receptors, is not produced in the embryo but in the neighboring endosperm. Subtilase-...
Source: ScienceNOW - January 23, 2020 Category: Science Authors: Doll, N. M., Royek, S., Fujita, S., Okuda, S., Chamot, S., Stintzi, A., Widiez, T., Hothorn, M., Schaller, A., Geldner, N., Ingram, G. Tags: Botany, Cell Biology reports Source Type: news
Scientists Confirm That Stress Can Indeed Turn Hair Grey
When Ya-Chieh Hsu, professor of stem cell and regenerative biology at Harvard University and the Harvard Stem Cell Institute, wanted to figure out exactly what makes hair turn grey, she started with an obvious, albeit anecdotal, culprit: stress. There are well-known historical examples of the connection between stress and hair greying—Marie Antoinette’s coif reportedly blanched after she was captured during the French Revolution—and studies have even linked stress in animals to greying hair. But for the first time, Hsu and her colleagues figured out the biological reason why stress saps the pigment out of...
Source: TIME: Health - January 22, 2020 Category: Consumer Health News Authors: Alice Park Tags: Uncategorized grey hair Stress Source Type: news
Researchers identify a possible cause and treatment for inflammatory bowel disease
(Chinese Academy of Sciences Headquarters) In a study published online in PNAS on Jan. 20, 2020, Prof. SUN Bing's team from the Center for Excellence in Molecular and Cellular Science, Institute of Biochemistry and Cell Biology of the Chinese Academy of Sciences, in collaboration with Prof. LIU Jie from Huashan Hospital, Fudan University, revealed a new mechanism involved in the pathogenesis of IBD and suggested therapeutic targets for clinical trial. (Source: EurekAlert! - Medicine and Health)
Source: EurekAlert! - Medicine and Health - January 21, 2020 Category: International Medicine & Public Health Source Type: news
Correlative three-dimensional super-resolution and block-face electron microscopy of whole vitreously frozen cells
Within cells, the spatial compartmentalization of thousands of distinct proteins serves a multitude of diverse biochemical needs. Correlative super-resolution (SR) fluorescence and electron microscopy (EM) can elucidate protein spatial relationships to global ultrastructure, but has suffered from tradeoffs of structure preservation, fluorescence retention, resolution, and field of view. We developed a platform for three-dimensional cryogenic SR and focused ion beam–milled block-face EM across entire vitreously frozen cells. The approach preserves ultrastructure while enabling independent SR and EM workflow optimizati...
Source: ScienceNOW - January 16, 2020 Category: Science Authors: Hoffman, D. P., Shtengel, G., Xu, C. S., Campbell, K. R., Freeman, M., Wang, L., Milkie, D. E., Pasolli, H. A., Iyer, N., Bogovic, J. A., Stabley, D. R., Shirinifard, A., Pang, S., Peale, D., Schaefer, K., Pomp, W., Chang, C.-L., Lippincott-Schwartz, J., Tags: Cell Biology, Physics r-articles Source Type: news
Lipid-gated monovalent ion fluxes regulate endocytic traffic and support immune surveillance
Despite ongoing (macro)pinocytosis of extracellular fluid, the volume of the endocytic pathway remains unchanged. To investigate the underlying mechanism, we used high-resolution video imaging to analyze the fate of macropinosomes formed by macrophages in vitro and in situ. Na+, the primary cationic osmolyte internalized, exited endocytic vacuoles via two-pore channels, accompanied by parallel efflux of Cl– and osmotically coupled water. The resulting shrinkage caused crenation of the membrane, which fostered recruitment of curvature-sensing proteins. These proteins stabilized tubules and promoted their elongation, d...
Source: ScienceNOW - January 16, 2020 Category: Science Authors: Freeman, S. A., Uderhardt, S., Saric, A., Collins, R. F., Buckley, C. M., Mylvaganam, S., Boroumand, P., Plumb, J., Germain, R. N., Ren, D., Grinstein, S. Tags: Cell Biology reports Source Type: news
Water loss regulates cell and vesicle volume
Source: ScienceNOW - January 16, 2020 Category: Science Authors: King, J. S., Smythe, E. Tags: Cell Biology perspective Source Type: news
How safe is a popular gene therapy vector?
Source: ScienceNOW - January 9, 2020 Category: Science Authors: Kaiser, J. Tags: Cell Biology, Medicine, Diseases In Depth Source Type: news
China delivers verdict on gene editing of babies
Source: ScienceNOW - January 9, 2020 Category: Science Authors: Cohen, J., Normille, D. Tags: Asia/Pacific News, Cell Biology, Scientific Community In Depth Source Type: news
Dermal sheath contraction powers stem cell niche relocation during hair cycle regression
Tissue homeostasis requires the balance of growth by cell production and regression through cell loss. In the hair cycle, during follicle regression, the niche traverses the skin through an unknown mechanism to reach the stem cell reservoir and trigger new growth. Here, we identify the dermal sheath that lines the follicle as the key driver of tissue regression and niche relocation through the smooth muscle contractile machinery that generates centripetal constriction force. We reveal that the calcium-calmodulin–myosin light chain kinase pathway controls sheath contraction. When this pathway is blocked, sheath contra...
Source: ScienceNOW - January 9, 2020 Category: Science Authors: Heitman, N., Sennett, R., Mok, K.-W., Saxena, N., Srivastava, D., Martino, P., Grisanti, L., Wang, Z., Maayan, A., Rompolas, P., Rendl, M. Tags: Cell Biology, Development r-articles Source Type: news
Glucose-dependent control of leucine metabolism by leucyl-tRNA synthetase 1
Despite the importance of glucose and amino acids for energy metabolism, interactions between the two nutrients are not well understood. We provide evidence for a role of leucyl-tRNA synthetase 1 (LARS1) in glucose-dependent control of leucine usage. Upon glucose starvation, LARS1 was phosphorylated by Unc-51 like autophagy activating kinase 1 (ULK1) at the residues crucial for leucine binding. The phosphorylated LARS1 showed decreased leucine binding, which may inhibit protein synthesis and help save energy. Leucine that is not used for anabolic processes may be available for catabolic pathway energy generation. The LARS1...
Source: ScienceNOW - January 9, 2020 Category: Science Authors: Yoon, I., Nam, M., Kim, H. K., Moon, H.-S., Kim, S., Jang, J., Song, J. A., Jeong, S. J., Kim, S. B., Cho, S., Kim, Y., Lee, J., Yang, W. S., Yoo, H. C., Kim, K., Kim, M.-S., Yang, A., Cho, K., Park, H.-S., Hwang, G.-S., Hwang, K. Y., Han, J. M., Kim, J. Tags: Cell Biology, Physiology reports Source Type: news
New MPMI focus issue seeks to improve management of virus-induced disease in crops
(American Phytopathological Society) The January focus issue of the Molecular Plant-Microbe Interactions journal includes four reviews and several research articles covering a variety of current topics examining the cell biology of virus-plant and virus-vector interactions, including cellular RNA hubs, plasmodesmal functioning, tripartite interactions, mechanisms of host defense suppression, and biotechnological approaches to induce host resistance. (Source: EurekAlert! - Biology)
Source: EurekAlert! - Biology - January 8, 2020 Category: Biology Source Type: news
The Advances that Will Shape Life Sciences in the 2020s
Systems biologist Steven Wiley says advancements in two areas--single-cell biology and CRISPR--are poised to transform research. (Source: The Scientist)
Source: The Scientist - January 3, 2020 Category: Science Tags: News & Opinion Source Type: news
TTC5 mediates autoregulation of tubulin via mRNA degradation
Tubulins play crucial roles in cell division, intracellular traffic, and cell shape. Tubulin concentration is autoregulated by feedback control of messenger RNA (mRNA) degradation via an unknown mechanism. We identified tetratricopeptide protein 5 (TTC5) as a tubulin-specific ribosome-associating factor that triggers cotranslational degradation of tubulin mRNAs in response to excess soluble tubulin. Structural analysis revealed that TTC5 binds near the ribosome exit tunnel and engages the amino terminus of nascent tubulins. TTC5 mutants incapable of ribosome or nascent tubulin interaction abolished tubulin autoregulation a...
Source: ScienceNOW - January 2, 2020 Category: Science Authors: Lin, Z., Gasic, I., Chandrasekaran, V., Peters, N., Shao, S., Mitchison, T. J., Hegde, R. S. Tags: Biochemistry, Cell Biology reports Source Type: news
A Kelch13-defined endocytosis pathway mediates artemisinin resistance in malaria parasites
In this study, we identified proteins located at a Kelch13-defined compartment. Inactivation of eight of these proteins, including Kelch13, rendered parasites resistant to ART, revealing a pathway critical for resistance. Functional analysis showed that these proteins are required for endocytosis of hemoglobin from the host cell. Parasites with inactivated Kelch13 or a resistance-conferring Kelch13 mutation displayed reduced hemoglobin endocytosis. ARTs are activated by degradation products of hemoglobin. Hence, reduced activity of Kelch13 and its interactors diminishes hemoglobin endocytosis and thereby ART activation, re...
Source: ScienceNOW - January 2, 2020 Category: Science Authors: Birnbaum, J., Scharf, S., Schmidt, S., Jonscher, E., Hoeijmakers, W. A. M., Flemming, S., Toenhake, C. G., Schmitt, M., Sabitzki, R., Bergmann, B., Fröhlke, U., Mesen-Ramirez, P., Blancke Soares, A., Herrmann, H., Bartfai, R., Spielmann, T. Tags: Cell Biology, Microbiology r-articles Source Type: news
Gene expression regulated by RNA stability
Source: ScienceNOW - January 2, 2020 Category: Science Authors: Shoshani, O., Cleveland, D. W. Tags: Cell Biology perspective Source Type: news
How cells learn to 'count'
(Johns Hopkins Medicine) One of the wonders of cell biology is its symmetry. Mammalian cells have one nucleus and one cell membrane, and most humans have 23 pairs of chromosomes. (Source: EurekAlert! - Medicine and Health)
Source: EurekAlert! - Medicine and Health - December 30, 2019 Category: International Medicine & Public Health Source Type: news
Researchers identify new therapeutic target for colorectal cancer
(Rockefeller University Press) Researchers at the University of Toronto have identified a key protein that supports the growth of many colorectal cancers. The study, which will be published Dec. 27 in the Journal of Cell Biology, reveals that a protein called Importin-11 transports the cancer-causing proteinβcatenin into the nucleus of colon cancer cells, where it can drive cell proliferation. Inhibiting this transport step could block the growth of most colorectal cancers caused by elevatedβcatenin levels. (Source: EurekAlert! - Medicine and Health)
Source: EurekAlert! - Medicine and Health - December 27, 2019 Category: International Medicine & Public Health Source Type: news
Targeting cholesterol metabolism in macrophages to eliminate viral infection
(Chinese Academy of Sciences Headquarters) A new study published in Immunity now provides important new information. WANG Hongyan's team from the Center for Excellence in Molecular and Cellular Science, Institute of Biochemistry and Cell Biology of the Chinese Academy of Sciences (CAS), in collaboration with Prof. WEI Bin at Shanghai University (the former PI of the Wuhan Institute of Virology of CAS), screened expression levels of multiple enzymes that regulate cholesterol metabolism to better understand how cholesterol metabolites combats infection. (Source: EurekAlert! - Medicine and Health)
Source: EurekAlert! - Medicine and Health - December 27, 2019 Category: International Medicine & Public Health Source Type: news