Researchers link cellular transport pathway to aggressive brain cancer
(Rockefeller University Press) Researchers at McGill University have identified a new cellular pathway that limits the growth and spread of brain tumors by controlling the recycling of cell surface receptor proteins. The study, which will be published January 14 in the Journal of Cell Biology (JCB), suggests that the pathway, which involves a protein called Rab35, is defective in many patients with glioblastoma and that restoring Rab35's activity could be a new therapeutic strategy for this deadly form of brain cancer. (Source: EurekAlert! - Cancer)
Source: EurekAlert! - Cancer - January 14, 2021 Category: Cancer & Oncology Source Type: news
Senolysis by glutaminolysis inhibition ameliorates various age-associated disorders
Removal of senescent cells (senolysis) has been proposed to be beneficial for improving age-associated pathologies, but the molecular pathways for such senolytic activity have not yet emerged. Here, we identified glutaminase 1 (GLS1) as an essential gene for the survival of human senescent cells. The intracellular pH in senescent cells was lowered by lysosomal membrane damage, and this lowered pH induced kidney-type glutaminase (KGA) expression. The resulting enhanced glutaminolysis induced ammonia production, which neutralized the lower pH and improved survival of the senescent cells. Inhibition of KGA-dependent glutamino...
Source: ScienceNOW - January 14, 2021 Category: Science Authors: Johmura, Y., Yamanaka, T., Omori, S., Wang, T.-W., Sugiura, Y., Matsumoto, M., Suzuki, N., Kumamoto, S., Yamaguchi, K., Hatakeyama, S., Takami, T., Yamaguchi, R., Shimizu, E., Ikeda, K., Okahashi, N., Mikawa, R., Suematsu, M., Arita, M., Sugimoto, M., Nak Tags: Cell Biology reports Source Type: news
Cryo-EM structure of the B cell co-receptor CD19 bound to the tetraspanin CD81
Signaling through the CD19-CD81 co-receptor complex, in combination with the B cell receptor, is a critical determinant of B cell development and activation. It is unknown how CD81 engages CD19 to enable co-receptor function. Here, we report a 3.8-angstrom structure of the CD19-CD81 complex bound to a therapeutic antigen-binding fragment, determined by cryo–electron microscopy (cryo-EM). The structure includes both the extracellular domains and the transmembrane helices of the complex, revealing a contact interface between the ectodomains that drives complex formation. Upon binding to CD19, CD81 opens its ectodomain ...
Source: ScienceNOW - January 14, 2021 Category: Science Authors: Susa, K. J., Rawson, S., Kruse, A. C., Blacklow, S. C. Tags: Biochemistry, Cell Biology reports Source Type: news
Noncanonical transnitrosylation network contributes to synapse loss in Alzheimers disease
Here we describe mechanistically distinct enzymes (a kinase, a guanosine triphosphatase, and a ubiquitin protein hydrolase) that function in disparate biochemical pathways and can also act in concert to mediate a series of redox reactions. Each enzyme manifests a second, noncanonical function—transnitrosylation—that triggers a pathological biochemical cascade in mouse models and in humans with Alzheimer’s disease (AD). The resulting series of transnitrosylation reactions contributes to synapse loss, the major pathological correlate to cognitive decline in AD. We conclude that enzymes with distinct primary...
Source: ScienceNOW - January 14, 2021 Category: Science Authors: Nakamura, T., Oh, C.-k., Liao, L., Zhang, X., Lopez, K. M., Gibbs, D., Deal, A. K., Scott, H. R., Spencer, B., Masliah, E., Rissman, R. A., Yates, J. R., Lipton, S. A. Tags: Cell Biology, Medicine, Diseases, Online Only r-articles Source Type: news
Phylodynamics for cell biologists
Multicellular organisms are composed of cells connected by ancestry and descent from progenitor cells. The dynamics of cell birth, death, and inheritance within an organism give rise to the fundamental processes of development, differentiation, and cancer. Technical advances in molecular biology now allow us to study cellular composition, ancestry, and evolution at the resolution of individual cells within an organism or tissue. Here, we take a phylogenetic and phylodynamic approach to single-cell biology. We explain how "tree thinking" is important to the interpretation of the growing body of cell-level data and...
Source: ScienceNOW - January 14, 2021 Category: Science Authors: Stadler, T., Pybus, O. G., Stumpf, M. P. H. Tags: Cell Biology, Online Only review Source Type: news
Max Planck Society, Rockefeller University Press enter " read-and-publish " agreement
(Rockefeller University Press) Max Planck Digital Library (MPDL) has signed an unlimited " read-and-publish " transformative agreement with Rockefeller University Press (RUP) on behalf of the Max Planck Society. The agreement covers Open Access (OA) publishing of articles in RUP's three hybrid journals:Journal of Cell Biology (JCB),Journal of Experimental Medicine (JEM) andJournal of General Physiology (JGP). (Source: EurekAlert! - Medicine and Health)
Source: EurekAlert! - Medicine and Health - January 13, 2021 Category: International Medicine & Public Health Source Type: news
Decoy toxin harnessed to fight botulism
Source: ScienceNOW - January 7, 2021 Category: Science Authors: Servick, K. Tags: Cell Biology, Medicine, Diseases In Depth Source Type: news
Gene therapy beats premature-aging syndrome in mice
Source: ScienceNOW - January 7, 2021 Category: Science Authors: Kaiser, J. Tags: Cell Biology, Genetics, Medicine, Diseases In Depth Source Type: news
Tubulin glycylation controls axonemal dynein activity, flagellar beat, and male fertility
In this study, we generated a mouse model entirely lacking tubulin glycylation. Male mice were subfertile owing to aberrant beat patterns of their sperm flagella, which impeded the straight swimming of sperm cells. Using cryo–electron tomography, we showed that lack of glycylation caused abnormal conformations of the dynein arms within sperm axonemes, providing the structural basis for the observed dysfunction. Our findings reveal the importance of microtubule glycylation for controlled flagellar beating, directional sperm swimming, and male fertility. (Source: ScienceNOW)
Source: ScienceNOW - January 7, 2021 Category: Science Authors: Gadadhar, S., Alvarez Viar, G., Hansen, J. N., Gong, A., Kostarev, A., Ialy-Radio, C., Leboucher, S., Whitfield, M., Ziyyat, A., Toure, A., Alvarez, L., Pigino, G., Janke, C. Tags: Biochemistry, Cell Biology, Online Only r-articles Source Type: news
Wait for me: Cell biologists decipher signal that ensures no chromosome is left behind
(University of California - San Diego) UC San Diego cell biologists have found a key clue in the mystery of how chromosomes are inherited correctly every time a cell divides. Using a novel cell probe, they unraveled how a 'matchmaker' molecule stops cell division until components are ready to be split. Precise chromosome duplication is a key factor in proper cell division. If components are altered, even slightly, birth defects and certain cancers can result. (Source: EurekAlert! - Medicine and Health)
Source: EurekAlert! - Medicine and Health - January 6, 2021 Category: International Medicine & Public Health Source Type: news
Langer awarded prestigious PRAT fellowship
NIEHS trainee Lee Langer won a Postdoctoral Research Associate (PRAT) Program fellowship to further his studies in stem cell biology. (read more) (Source: Environmental Factor - NIEHS Newsletter)
Source: Environmental Factor - NIEHS Newsletter - January 6, 2021 Category: Environmental Health Source Type: news
Detecting oxygen changes in the lungs
Source: ScienceNOW - December 31, 2020 Category: Science Authors: Zacharias, W. Tags: Cell Biology, Molecular Biology perspective Source Type: news
Transcriptional control of proteostasis
Source: ScienceNOW - December 31, 2020 Category: Science Authors: Hurtley, S. M. Tags: Cell Biology, Medicine, Diseases twis Source Type: news
Protecting the lung from hypoxic stress
Source: ScienceNOW - December 31, 2020 Category: Science Authors: Purnell, B. A. Tags: Cell Biology, Molecular Biology twis Source Type: news
Airway stem cells sense hypoxia and differentiate into protective solitary neuroendocrine cells
Neuroendocrine (NE) cells are epithelial cells that possess many of the characteristics of neurons, including the presence of secretory vesicles and the ability to sense environmental stimuli. The normal physiologic functions of solitary airway NE cells remain a mystery. We show that mouse and human airway basal stem cells sense hypoxia. Hypoxia triggers the direct differentiation of these stem cells into solitary NE cells. Ablation of these solitary NE cells during hypoxia results in increased epithelial injury, whereas the administration of the NE cell peptide CGRP rescues this excess damage. Thus, we identify stem cells...
Source: ScienceNOW - December 31, 2020 Category: Science Authors: Shivaraju, M., Chitta, U. K., Grange, R. M. H., Jain, I. H., Capen, D., Liao, L., Xu, J., Ichinose, F., Zapol, W. M., Mootha, V. K., Rajagopal, J. Tags: Cell Biology, Molecular Biology r-articles Source Type: news
Interactions between nascent proteins translated by adjacent ribosomes drive homomer assembly
In this study, we investigated whether direct interaction of two nascent proteins, emerging from nearby ribosomes (co-co assembly), constitutes a general mechanism for oligomer formation. We used proteome-wide screening to detect nascent chain–connected ribosome pairs and identified hundreds of homomer subunits that co-co assemble in human cells. Interactions are mediated by five major domain classes, among which N-terminal coiled coils are the most prevalent. We were able to reconstitute co-co assembly of nuclear lamin in Escherichia coli, demonstrating that dimer formation is independent of dedicated assembly machi...
Source: ScienceNOW - December 31, 2020 Category: Science Authors: Bertolini, M., Fenzl, K., Kats, I., Wruck, F., Tippmann, F., Schmitt, J., Auburger, J. J., Tans, S., Bukau, B., Kramer, G. Tags: Cell Biology, Molecular Biology r-articles Source Type: news
A tripartite mechanism catalyzes Mad2-Cdc20 assembly at unattached kinetochores
During cell division, kinetochores couple chromosomes to spindle microtubules. To protect against chromosome gain or loss, kinetochores lacking microtubule attachment locally catalyze association of the checkpoint proteins Cdc20 and Mad2, which is the key event in the formation of a diffusible checkpoint complex that prevents mitotic exit. We elucidated the mechanism of kinetochore-catalyzed Mad2-Cdc20 assembly with a probe that specifically monitors this assembly reaction at kinetochores in living cells. We found that catalysis occurs through a tripartite mechanism that includes localized delivery of Mad2 and Cdc20 substr...
Source: ScienceNOW - December 31, 2020 Category: Science Authors: Lara-Gonzalez, P., Kim, T., Oegema, K., Corbett, K., Desai, A. Tags: Biochemistry, Cell Biology reports Source Type: news
CDC20 assists its catalytic incorporation in the mitotic checkpoint complex
Open (O) and closed (C) topologies of HORMA-domain proteins are respectively associated with inactive and active states of fundamental cellular pathways. The HORMA protein O-MAD2 converts to C-MAD2 upon binding CDC20. This is rate limiting for assembly of the mitotic checkpoint complex (MCC), the effector of a checkpoint required for mitotic fidelity. A catalyst assembled at kinetochores accelerates MAD2:CDC20 association through a poorly understood mechanism. Using a reconstituted SAC system, we discovered that CDC20 is an impervious substrate for which access to MAD2 requires simultaneous docking on several sites of the ...
Source: ScienceNOW - December 31, 2020 Category: Science Authors: Piano, V., Alex, A., Stege, P., Maffini, S., Stoppiello, G. A., Huis in t Veld, P. J., Vetter, I. R., Musacchio, A. Tags: Biochemistry, Cell Biology reports Source Type: news
QRICH1 dictates the outcome of ER stress through transcriptional control of proteostasis
Tissue homeostasis is perturbed in a diversity of inflammatory pathologies. These changes can elicit endoplasmic reticulum (ER) stress, protein misfolding, and cell death. ER stress triggers the unfolded protein response (UPR), which can promote recovery of ER proteostasis and cell survival or trigger programmed cell death. Here, we leveraged single-cell RNA sequencing to define dynamic transcriptional states associated with the adaptive versus terminal UPR in the mouse intestinal epithelium. We integrated these transcriptional programs with genome-scale CRISPR screening to dissect the UPR pathway functionally. We identifi...
Source: ScienceNOW - December 31, 2020 Category: Science Authors: You, K., Wang, L., Chou, C.-H., Liu, K., Nakata, T., Jaiswal, A., Yao, J., Lefkovith, A., Omar, A., Perrigoue, J. G., Towne, J. E., Regev, A., Graham, D. B., Xavier, R. J. Tags: Cell Biology, Medicine, Diseases, Online Only r-articles Source Type: news
A powerful computational tool for efficient analysis of cell division 4D image data
(City University of Hong Kong) A joint research team co-led by City University of Hong Kong (CityU) has developed a novel computational tool that can reconstruct and visualise three-dimensional (3D) shapes and temporal changes of cells, speeding up the analysing process from hundreds of hours by hand to a few hours by the computer. Revolutionising the way biologists analyse image data, this tool can advance further studies in developmental and cell biology, such as the growth of cancer cells. (Source: EurekAlert! - Medicine and Health)
Source: EurekAlert! - Medicine and Health - December 22, 2020 Category: International Medicine & Public Health Source Type: news
Top Technical Advances of 2020
The pandemic spurred innovation in a variety of ways, from CRISPR-based diagnostics to cell biology benchwork at home. (Source: The Scientist)
Source: The Scientist - December 18, 2020 Category: Science Tags: News & Opinion Source Type: news
Groundwork for COVID-19 Vaccine Laid at Dartmouth
Discoveries originating in a basic science lab at the Geisel School of Medicine are being used in the newly approved COVID-19 vaccine from the Pfizer/BioNTech partnership. (Source: News at Dartmouth Medical School)
Source: News at Dartmouth Medical School - December 17, 2020 Category: Hospital Management Authors: Timothy Dean Tags: News Press Release Research biochemistry cell biology COVID-19 vaccine Source Type: news
LSU health research suggests new mechanism to balance emotional behavior
(Louisiana State University Health Sciences Center) Research led by Si-Qiong June Liu, MD, PhD, Professor of Cell Biology and Anatomy at LSU Health New Orleans School of Medicine, discovered a surprising reciprocal interaction between chemicals in the brain resulting in accelerated loss of molecules that regulate brain cell communication. (Source: EurekAlert! - Medicine and Health)
Source: EurekAlert! - Medicine and Health - December 17, 2020 Category: International Medicine & Public Health Source Type: news
mRNA's next challenge: Will it work as a drug?
Source: ScienceNOW - December 17, 2020 Category: Science Authors: Servick, K. Tags: Cell Biology, Medicine, Diseases In Depth Source Type: news
A matter of balance: asymmetric divisions are crucial to form a functional retina
(Instituto Gulbenkian de Ciencia) Researchers at the Instituto Gulbenkian de Ci ê ncia and the Max Planck Institute of Molecular Cell Biology and Genetics in Dresden, Germany, have discovered that in the developing retina, and important part of the central nervous system, the divisions leading to the first differentiating neurons are asymmetric and that this asymmetry is necessary to generate the correct types of neurons in the right numbers and proportions. (Source: EurekAlert! - Biology)
Source: EurekAlert! - Biology - December 11, 2020 Category: Biology Source Type: news
Tweaking genes with CRISPR or viruses fixes blood disorders
Source: ScienceNOW - December 10, 2020 Category: Science Authors: Kaiser, J. Tags: Cell Biology, Medicine, Diseases In Depth Source Type: news
Developmental clock and mechanism of de novo polarization of the mouse embryo
Embryo polarization is critical for mouse development; however, neither the regulatory clock nor the molecular trigger that it activates is known. Here, we show that the embryo polarization clock reflects the onset of zygotic genome activation, and we identify three factors required to trigger polarization. Advancing the timing of transcription factor AP-2 gamma (Tfap2c) and TEA domain transcription factor 4 (Tead4) expression in the presence of activated Ras homolog family member A (RhoA) induces precocious polarization as well as subsequent cell fate specification and morphogenesis. Tfap2c and Tead4 induce expression of ...
Source: ScienceNOW - December 10, 2020 Category: Science Authors: Zhu, M., Cornwall-Scoones, J., Wang, P., Handford, C. E., Na, J., Thomson, M., Zernicka-Goetz, M. Tags: Cell Biology, Development, Online Only r-articles Source Type: news
Janssen Submits Application to U.S. FDA Seeking Approval of Amivantamab for the Treatment of Patients with Metastatic Non-Small Cell Lung Cancer with EGFR Exon 20 Insertion Mutations
RARITAN, N.J., December 3, 2020 – The Janssen Pharmaceutical Companies of Johnson & Johnson announced today the submission of a Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA) seeking approval of amivantamab for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion mutations whose disease has progressed on or after platinum-based chemotherapy. The application marks the first-ever regulatory submission for the treatment of patients with NSCLC with EGFR exon 20 insertion mutations. The Company...
Source: Johnson and Johnson - December 3, 2020 Category: Pharmaceuticals Tags: Innovation Source Type: news
Discovery Against All Odds
Watch Nobel Laureate Rita Levi-Montalcini tell the story of how she continued her transformative cell biology research as World War II raged. (Source: The Scientist)
Source: The Scientist - December 1, 2020 Category: Science Tags: Videos Source Type: news
Abl and Canoe/Afadin mediate mechanotransduction at tricellular junctions
Epithelial structure is generated by the dynamic reorganization of cells in response to mechanical forces. Adherens junctions transmit forces between cells, but how cells sense and respond to these forces in vivo is not well understood. We identify a mechanotransduction pathway involving the Abl tyrosine kinase and Canoe/Afadin that stabilizes cell adhesion under tension at tricellular junctions in the Drosophila embryo. Canoe is recruited to tricellular junctions in response to actomyosin contractility, and this mechanosensitivity requires Abl-dependent phosphorylation of a conserved tyrosine in the Canoe actin-binding do...
Source: ScienceNOW - November 26, 2020 Category: Science Authors: Yu, H. H., Zallen, J. A. Tags: Cell Biology, Development, Online Only r-articles Source Type: news
Fetal mast cells mediate postnatal allergic responses dependent on maternal IgE
We report a role for MCs within the developing fetus and demonstrate that fetal MCs may contribute to antigen-specific vertical transmission of allergic disease. (Source: ScienceNOW)
Source: ScienceNOW - November 19, 2020 Category: Science Authors: Msallam, R., Balla, J., Rathore, A. P. S., Kared, H., Malleret, B., Saron, W. A. A., Liu, Z., Hang, J. W., Dutertre, C. A., Larbi, A., Chan, J. K. Y., St. John, A. L., Ginhoux, F. Tags: Cell Biology, Immunology r-articles Source Type: news
Tissue topography steers migrating Drosophila border cells
Moving cells can sense and respond to physical features of the microenvironment; however, in vivo, the significance of tissue topography is mostly unknown. Here, we used Drosophila border cells, an established model for in vivo cell migration, to study how chemical and physical information influences path selection. Although chemical cues were thought to be sufficient, live imaging, genetics, modeling, and simulations show that microtopography is also important. Chemoattractants promote predominantly posterior movement, whereas tissue architecture presents orthogonal information, a path of least resistance concentrated nea...
Source: ScienceNOW - November 19, 2020 Category: Science Authors: Dai, W., Guo, X., Cao, Y., Mondo, J. A., Campanale, J. P., Montell, B. J., Burrous, H., Streichan, S., Gov, N., Rappel, W.-J., Montell, D. J. Tags: Cell Biology, Development reports Source Type: news
Sponsored Collection | The Human Protein Atlas: A 20-year journey into the body
Source: ScienceNOW - November 19, 2020 Category: Science Tags: Cell Biology, Medicine, Diseases From the AAAS Office of Publishing Source Type: news
Identification of Potential Biomarkers and Immune Features of Sepsis Using Bioinformatics Analysis
This study revealed imbalanced immune responses at the transcriptomic level during early sepsis and identified nine genes as potential biomarkers for sepsis. (Source: Current Awareness Service for Health (CASH))
Source: Current Awareness Service for Health (CASH) - November 13, 2020 Category: Consumer Health News Source Type: news
Astrocytes identified as master 'conductors' of the brain
(Duke University) A team of Duke scientists has found that glial astrocytes are involved in regulating inhibitory synapses by binding to neurons through an adhesion molecule called NrCAM. 'We really discovered that the astrocytes are the conductors that orchestrate the notes that make up the music of the brain,' said Scott Soderling, PhD, chair of the Department of Cell Biology in the School of Medicine and senior author on the paper. (Source: EurekAlert! - Biology)
Source: EurekAlert! - Biology - November 12, 2020 Category: Biology Source Type: news
Cellular adaptation during metabolic stress
Source: ScienceNOW - November 12, 2020 Category: Science Authors: Hurtley, S. M. Tags: Cell Biology, Molecular Biology twis Source Type: news